Article - De Giovanni — USA v. Jittaphol (Dkt. 70-5, D. Mass.)

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U.S. District Court for the District of Massachusetts · No. 1:21-cr-10270-MLW · Doc. 70-5 · 2022-04-06 · Docket on CourtListener

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Current Medicinal Chemistry, 2013, 20, 545-561 
545 
The Current Status of Sweat Testing For Drugs of Abuse: A Review 
N. De Giovanni* and N. Fucci 
Institute of Legal Medicine, Catholic University of Sacred Heart, L.go Francesco Vito, 1 00168 Rome, Italy 
Abstract: Sweat is an alternative biological matrix useful to detect drugs of abuse intake. It is produced by eccrine and apocrine glands 
originating in the skin dermis and terminating in secretory canals that flow into the skin surface and hair follicles. Since many years it has 
been demonstrated that endogenous and exogenous chemicals are secreted in this biological sample hence its collection and analysis 
could show the past intake of xenobiotics. From the seventies the excretion of drugs of abuse has been investigated in human skin excre-
tion; later in nineties forensic scientists began to experiment some techniques to trap sweat for analyses. Even if the use of skin excretions 
for drug testing has been restricted mainly by difficulties in sample recovery, the marketing of systems for the sample collection has al-
lowed successful sweat testing for several drugs of abuse. In the recent years sweat testing developed a noninvasive monitoring of drug 
exposure in various contexts as criminal justice, employment and outpatient clinical settings. This paper provides an overview of litera-
ture data about sweat drug testing procedures for various xenobiotics especially cocaine metabolites, opiates, cannabis and ampheta-
mines. Issues related to collection, analysis and interpretation of skin excretions as well as its advantages and disadvantages are dis-
cussed. Moreover the chance to apply the technique to some particular situation such as workplace drug testing, drivers, doping or prena-
tal diagnosis, the comparison between sweat and other non conventional matrices are also reviewed. According to literature data the 
analysis of sweat may be usefully alternative for verifying drug history and for monitoring compliance. 
Keywords: Sweat testing, drugs of abuse, unconventional matrix. 
1. INTRODUCTION 
The diagnosis of acute intoxication by xenobiotics, together 
with the determination of drug use/abuse is the target of forensic 
toxicology. Analysis of biological fluids and tissues provides the 
most objective method for documenting human drug exposure. The 
choice of biological matrices is the crucial step for a correct inves-
tigation, because each biological specimen is unique and offers a 
somewhat different pattern of information regarding drug use over 
time. The toxicologist needs a deep knowing of various parameters 
such as the purpose of the investigation, the kind of substances to 
be identified, the time, way and modality of intake, the knowledge 
of pharmacokinetic and pharmacodynamic of drugs [1].  
Blood and urine are historically the biological matrices more 
employed for testing of drugs of abuse both of cadavers and living 
people. However, currently there is growing interest in the use of 
alternative body fluids and tissues such as saliva, skin excretions 
and hair for the diagnosis of drug use [2-7]. The purpose of these 
studies was the exploration of less invasive collectors in order to 
obtain more information regarding the use/abuse of psychotropic 
drugs. Research may involve the detection of the parent compound 
or metabolites and sensitivity, specificity, and reliability of drug 
testing may vary depending on the drug [7]. Scientific international 
literature developed analytical methodologies to detect xenobiotics 
on sweat, matrix in which illicit compounds can be found with a 
time window that allows peculiar information different from other 
biological samples [8]. 
As referred by Kintz P. [9] since 1911 researchers established 
that drugs are excreted by the body in sweat, but many analytical 
and practical problems mainly due to the difficulty in collecting 
skin excretions, did not allow its application in forensic toxicology 
until 1990s. In 1980 Phillips M. [10] devised an occlusive adhesive 
patch that trapped solute and water components in sweat providing 
a possible means to monitor patient compliance with therapeutic 
regimens. The patch consisted of an absorbent pad impregnated 
with sodium chloride crystals under a water-proof dressing. Later, 
occlusive bandages, consisting of one to three layers of filter papers 
or pieces of cotton, gauze, or towel were proposed to collect sweat 
[9, 11]. Significant advances have been made in the past years to 
 
*Address correspondence to this author at the Institute of Legal Medicine, Catholic 
University of Sacred Heart, L.go Francesco Vito, 1 00168 Rome, Italy; Tel: 0039 6 
35507031; Fax: 0039 6 3051168; E-mail: nadia.degiovanni@rm.unicatt.it 
develop a sweat-patch technology. In fact a non occlusive sweat 
collection device (patch) was developed by a commercial firm (Su-
dormed, Santa Ana, CA, USA) in 1990. 
The variation between individuals in the amount of sweat they 
excreted has caused difficulty for those attempting to construct a 
universal sweat collection device. Earlier experiments to test for the 
presence of specific substances in sweat have used patches that 
occlude the skin causing numerous problems such as skin irritation, 
alteration of both the steady-state, pH of the skin and the skin’s 
colonizing bacteria [12]. Newer non occlusive patches use a trans-
parent film that allows oxygen, carbon dioxide and water vapor to 
escape, while trapping the necessary traces of drug use excreted in 
sweat [13]. Cone E.J. [8] found many benefits in using this type of 
patch, including high subject acceptability, low incidence of aller-
gic reactions to the patch adhesive and ability to monitor drug in-
take for a period of several weeks with a single patch. Several stud-
ies have also found that the patch is resistant to inconspicuous tam-
pering [8, 12, 14]. Kintz P. et al. [12] also reported that no special 
precautions were needed to wear the patches for several days except 
to avoid excessive towel rubbing after bathing. Hence, success in 
sweat testing for several drugs of abuse has been accomplished 
because of substantial advances in sample collection and improved 
accuracy of measurement methods. Consequently remarkable ad-
vances in sensitive analytical techniques have enabled the analysis 
of drugs in unconventional samples such as skin excretions.  
Some reviews regarding the employ of alternative biological 
matrices were published in different periods. The first paper found 
in literature [15] referred about the detection of drugs of abuse in 
hair, nail, saliva and sweat. Preparation or pretreatment of samples, 
analytical procedures, and the interpretation of analytical results are 
discussed concomitantly. 
A monographic report of NIDA was published in the year 1997 
by Cone E.J. [8]. The usefulness of various biological fluids, in-
cluding sweat, together with the chemical and physical properties 
was discussed. Research of sweat testing for drugs had been limited 
because of the difficulty in collecting sweat samples and the author 
suggests the employ of a sweat collection device that appeared to 
offer promise for the collection of this sample. He refers about the 
advantages of the sweat patch for drug monitoring that include the 
high subject acceptability of wearing the patch, low incidence of 
allergic reactions to the patch adhesive and ability to monitor drug 
intake for a period of several weeks for the single patch.  
 
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© 2013 Bentham Science Publishers 
Case 1:21-cr-10270-MLW     Document 70-5     Filed 04/06/22     Page 1 of 17

546    Current Medicinal Chemistry,  2013, Vol. 20, No. 4 
De Giovanni and Fucci 
A review referring on the detection of marijuana, cocaine, opi-
ates, amphetamines, benzodiazepines, barbiturates, phencyclidine 
and nicotine in sweat is reported with emphasis on forensic applica-
tions [16]. Sweat maybe applicable for use in driving while intoxi-
cated and surveying populations for illicit drug use. The review 
refers about advantages and disadvantages of sweat testing com-
pared to saliva and urine.  
Huestis MA et al. [11] in 1999 reviewed the detection of co-
caine, codeine and metabolites in sweat by GC/MS detailing results 
from a new type of sweat collection device that allows rapid collec-
tion of sweat samples. 
Various aspects concerning the practical application and foren-
sic interpretation of data obtained by drug monitoring from the skin 
surface are discussed by Skopp G. et al. [17]. Basic information on 
the composition of skin secretions and their particular transport 
mechanisms, as far as known, are given. Drug molecules from 
blood are considered to reach the skin surface by various routes 
such as by sweat and sebum as well as by inter- and/or trans-
cellular diffusion. The role of the stratum corneum as a temporary 
drug reservoir exceeding positive drug findings in urine is outlined.  
Cone E.J. in 2001 [18] provided an overview of global drug 
trafficking patterns and drug use, and results from a survey of legal 
statutes in twenty countries covering use of alternate matrices for 
drug testing. He stated that advances have also been made in the use 
of alternate biological matrices such as sweat for drug testing. Do-
lan K. et al. [19] published a brief overview providing qualitative 
drug testing procedures using sweat; authors stated that sweat may 
be useful in the detection of illicit drug use for developments in 
patch technology which allows for a cumulative estimate of drug 
exposure over several days. In the year 2010 Maurer H.H. [20] 
published an important review on analytical toxicology describing 
the procedures for screening, identification and quantification of 
drugs, poisons and their metabolites in various matrices including 
sweat. The paper focused on the selection of the most appropriate 
bio-sample to be analyzed depending of the task to be fulfilled.  
The authors of the present review believe useful to briefly refer 
about the employ of sweat in clinical settings. Shearer D.S. et al. in 
1998 [21] performed a drug testing of patients in a psychiatric out-
patient service allowing to identify patients who relapse into re-
newed use of drugs of abuse and in monitoring the effectiveness of 
ongoing medical and psychological therapy. Moreover DuPont RL. 
[22] proposed sweat for clinical settings and affirmed it could be 
useful in schools and in-family based efforts to prevent drug use. 
This review focuses the attention on skin excretions that may 
provide an additional tool for monitoring drug use. Although the 
use of sweat for drug testing has been hampered by difficulties in 
sample collection and sensitivity of analytical methods, successful 
sweat testing for several drugs of abuse has been accomplished 
because of substantial advances facilitating sample collection and 
improving the accuracy of diagnostic techniques [8].  
For this purpose a computerized search of articles inserted in 
“PUBMED” and ”SCOPUS” from 1992 to 2011 was performed. 
100 papers were chosen including some reviews for their relevance 
on sweat technology (Table 1). The articles reviewed were sched-
uled on the basis of the population studied and/or the referred appli-
cation (clinical setting, forensic application, workplace drug testing, 
pregnancy, controlled administration, roadside testing, etc).  
2. HUMAN SWEAT 
Human sweat is a biological fluid and its secretion is an impor-
tant homeostatic mechanism for maintaining a constant core body 
temperature to a narrow physiological range [11]. Randall W.C. in 
1953 [23] stated that at temperatures above 31°C body heat is dissi-
pated by the release of sweat on the skin surface resulting in evapo-
rative heat loss however a loss by sweating can also occur at other 
temperatures. Eichna L.W. [24] asserted that the amount of sweat 
secreted is highly variable and dependent upon daily activity, emo-
tional state and environmental temperature. Sweat is eliminated 
from human body through the skin that consists of two layers; the 
outer epidermis and the inner dermis. The epidermis in turn is com-
posed of two main cell types, the pigmented melanocytes which 
protect against damaging effects of sunlight, and keratocytes which 
contain the filaments that provide the structural integrity of the skin. 
As keratocytes mature they lose their cell nucleus and move to the 
outer portion of the skin; hence this layer (called stratum corneum) 
consists entirely of keratocytes that have lost their nuclei. The un-
derlying dermis, which makes up the bulk of the skin is composed 
of fibrous well vascularized connective tissue and it contains the 
hair follicles, sweat and sebaceous glands [25]. Under the dermis 
there is the adipose layer that consists of lobules of fat separated by 
fibrous connective tissue. Blood vessels pass into and through this 
layer. Sweat is approximately 99% water with the most concen-
trated solute being sodium chloride. The rate of sweating is highly 
dependent upon environmental temperatures and rates as high as 3 
l/min have been recorded for short periods [2]. The majority of 
sweat is produced by eccrine glands located in the transdermal layer 
of most skin surfaces. Apocrine glands are an other type of sweat 
gland located in specific regional areas like the skin of the axilla, 
pubic region and around the nipples. Sweat glands often develop in 
close association with hair follicles and sometimes empty directly 
into hair follicles. Approximately 50% of the total volume of sweat 
is produced by the trunk, 25% by the legs and 25% by the head and 
upper extremities [2]. Besides aqueous secretion, the skin is also 
bathed with sebaceous secretions especially on the face and scalp. 
The sebaceous secretions are primarily lipids that may transport and 
adsorb many drugs [16].  
Sweat and sebaceous glands are housed in the dermis and are 
distributed through the body disproportionately. The highest con-
centration of sweat glands resides in the hands, while the forehead 
contains the densest population of sebaceous glands [26]. Moisture 
maybe lost from the skin by either insensible sweat likely caused by 
diffusion through the skin and sensible sweat which is actively 
excreted during stress and exercise [16]. Several reports have dem-
onstrated the sweat is suitable alternative biological matrix for 
monitoring recent drug use because a small but sufficient fraction 
of the drug is excreted by the skin [8, 20, 25]. 
3. EXCRETION OF XENOBIOTICS INTO SWEAT 
The excretion of drugs in sweat has important implications in 
clinical and forensic toxicology as well as in preventative medicine. 
Specific and sensitive detection or precise quantification of xenobi-
otics in bio-samples are great challenges in analytical toxicology. 
Investigators have been studying the secretion of endogenous and 
exogenous chemicals in sweat for many years. The sebaceous se-
cretion is primarily constituted by lipids that may transport and 
absorb many drugs. Different concentrations of drugs may be ex-
pected, depending upon the area of the body in which the sample is 
taken, because fat-soluble drugs may be sequestered or secreted by 
the skin. The mechanism by which drugs are incorporated into 
sweat is not fully understood [27] and there are several potential 
mechanisms by which drugs may be secreted in sweat including 
passive diffusion from blood into sweat glands and transdermal 
migration of drugs across the skin [2]. Non-ionized basic drugs 
diffuse into sweat and become ionized as a result of the lower pH of 
sweat as compared to blood [28]. The pH of sweat is generally in 
the range of 4 to 6.8, with the average sweat pH from resting indi-
viduals considered to be 5.8. With the increased flow rate (follow-
ing exercise or above 31°C), sweat pH has been found to increase 
to 6.8 [8, 28]. A low basal pH should favor concentration of basic 
drugs in sweat thus producing a free-drug sweat/plasma (S/P) ratio 
greater than 1. This assumption is supported by studies of the excre-
tion of ammonia in sweat. The observed S/P ratios for total ammo-
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Sweat Testing for Drugs of Abuse 
Current Medicinal Chemistry,  2013, Vol. 20, No. 4      547 
Table 1. 
Drugs of Abuse in Sweat: Crucial Aspects of Methodology 
 
Reference 
Author 
Drugs and Metabolites 
Collection Device 
Modality and Time of 
Wear 
Analytical 
Method 
Other Matrices 
Application 
[2] 
Cone EJ. et al. 1994 
heroin and cocaine 
Sudormed/Band-
aid 
Back, Abdomen / 0-3 
Days 
GC/MS 
urine, hair 
Clinical setting 
[3] 
Smith FP. et al. 1996 
cocaine 
Sweat wipes 
forehead skin swabs 
RIA-GC/MS 
hair, saliva, urine 
Drug users and 
children 
[4] 
Kidwell DA. et al. 1997 
cocaine 
Sweat wipes 
wiping forehead 
GC/MS/MS 
hair 
University popula-
tion 
[5] 
De Oliveira CDR. et al. 
2007 
 
 
 
GC/MS LC/MS 
saliva, hair, nails, 
Review of chroma-
tographic proce-
dures 
[7] 
Vearrier D. et al. 2010 
 
 
 
 
various 
Review of biologi-
cal matrices 
[8] 
Cone EJ. 1997 
 
 
 
 
 
Monography 
[9] 
Kintz P. 1996 
opiates, cocaine, can-
nabinoids, buprenor-
phine, metadone, nordi-
azepam 
PharmChek 
back / 1 week 
GC/MS 
urine, hair 
Clinical setting 
[11] 
Huestis M. et al. 1999 
cocaine , codeine 
Sudormed/Fast 
Patch 
palm, torso / 30 minutes 
GC/MS 
 
Review of sweat 
testing 
[12] 
Kintz P. el al 1997 
opiates 
PharmChek 
back /24 hours 
GC/MS 
no 
Clinical setting 
[13] 
Kidwell DA. et al. 2001 
cocaine, metampheta-
mine, heroin 
PharmCheck 
arms 
GC/MS 
no 
Environmental 
contamination 
[14] 
Caplan YH. et al. 2001 
 
 
 
 
hair, nail, blood , 
urine 
Workplace drug 
testing 
[15] 
Inoue T. el al 1992 
 
 
 
 
 
Review of biologi-
cal matrices 
[16] 
Kidwell DA. et al. 1998 
 
 
 
 
saliva 
Review - Forensic 
[17] 
Skopp G. et al. 1999 
 
 
 
 
saliva 
Review- Roadside 
testing 
[18] 
Cone EJ. 2001 
 
 
 
 
 
Review- Workplace 
drug testing 
[19] 
Dolan K. et al. 2004 
 
 
 
 
urine, hair, saliva 
Review- Forensic 
[20] 
Maurer HH. 2010 
 
 
 
 
urine, blood, tissues, 
hair, oral fluid, 
nails, meconium 
Review of analytical 
toxicology 
[21] 
Shearer DS. et al. 1998 
 
 
 
 
urine,saliva, hair, 
urine 
Review of biologi-
cal matrices, Psy-
chiatric 
[22] 
DuPont RL. 2010 
 
 
 
 
hair, saliva, urine 
General aspects, 
Clinical setting 
[25] 
Levisky JA et al. 2000 
cocaine, opiates 
Adipose tissue. 
skin 
skin collected during 
autopsy 
GC/MS 
blood 
Autoptical data 
[26] 
Chawarski MC et al. 2007 
opiates 
PharmCheck 
not specify 
GC/MS 
urine 
Clinical setting 
[27] 
Brunet BR et al. 2010 
cocaine, opiates 
PharmCheck 
back. arm /1 week 
GC/MS 
no 
Pregnancy 
[28] 
Huestis MA etal 1998 
 
 
 
 
alternative matrices 
Monography 
[30] 
Kacinko S.L. et al. 2005 
cocaine 
PharmCheck 
back, abdomen / 4-15 
hours 
GC/MS 
no 
Controlled 
administration 
[31] 
Uemura N. et al. 2004 
cocaine 
PharmCheck 
back, shoulder / 1-72 
hours 
GC/MS 
no 
Controlled 
administration 
[32] 
Schwilke EW.et al. 2006 
opiates 
PharmCheck 
abdomen, back / 1 
week, 1-15 hours 
GC/MS 
no 
Controlled 
administration 
[34] 
Faergermann J. et al. 1993 
terbinafine 
stratum corneum, 
dermis-epidermis, 
sebum 
 
 
hair, nails,  plasma 
Controlled admini-
stration 
[35] 
Burns M. et al. 1995 
cocaine 
Band-aid 
torso, biceps, back / 1 
week 
 
urine 
Clinical setting 
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548    Current Medicinal Chemistry,  2013, Vol. 20, No. 4 
De Giovanni and Fucci 
(Table 1) contd… 
Reference 
Author 
Drugs and Metabolites Collection Device 
Modality and Time of 
Wear 
Analytical 
Method 
Other Matrices 
Application 
[36] 
Joseph RE. et al. 1998 
cocaine, opiates 
Sebutape 
back, forehead /1-2 
hours 
GC/MS 
plasma, sebum,   
stratum corneum 
Controlled 
administration 
[37] 
Liberty HJ. et al. 2004 
cocaine 
PharmCheck 
biceps/ various time 
GC/MS 
urine 
Controlled admini-
stration 
[38] 
Kidwell DA. et al. 2003 
cocaine 
PharmChek-Skin 
swabs 
arms /1-4 weeks 
immunoassay 
(CEDIA, Co-
zart,OraSure 
ELISA) - GC/MS 
urine 
Environmental 
contamination 
[39] 
Pichini  S.  et al. 2003 
MDMA 
PharmCheck-
Drugwipe 
24 hours (back) 
immunoassay - 
GC/MS 
urine 
Controlled 
administration 
[40] 
Balabanova S. et al. 1992 
cocaine, morphine, 
methadone 
Pilocarpine stimu-
lation 
 
RIA 
 
Drugs users 
[42] 
Spiehler V. et al. 1996 
cocaine 
PharmChek 
skin  / 7 days 
Immunoassay-
GC/MS 
no 
Drugs users, con-
trolled administra-
tion 
[43] 
Burns M. et al. 1995 
cocaine 
PharmChek/Band-
aid 
up to 7 days 
RIA-GC/MS 
no 
Controlled admini-
stration 
[44] 
Skopp G. et al. 1996 
theophylline, metha-
done, heroin , cocaine 
Sudormed 
 
 
 
Controlled admini-
stration 
[45] 
Kintz P. et al. 1996 
diazepam 
Sudormed 
0-72 hours 
GC/MS 
no 
Controlled 
administration 
[46] 
Kintz P. et al. 1996 
codeine, phenobarbital 
Sudormed 
different sites / up to 7 
days 
GC/MS 
 
Controlled admini-
stration 
[47] 
Liberty  HJ. Et al 2003 
crack 
PharmChek, 
Fastpatch 
one per hand /15-30 
minutes 
GC/MS 
urine 
Controlled 
administration 
[48] 
Fogerson R. et al. 1997 
opiates 
PharmChek 
skin /1-10 day 
EIA-GC/MS 
urine 
Controlled admini-
stration, adulteration 
study 
[50] 
Moody DE. et al. 2001 
cocaine, heroin 
PharmChek 
 
RIA /EIA 
no 
In vitro study 
[51] 
Moody DE. et al. 2004 
cocaine 
PharmChek 
 
RIA/GC/MS 
 
Controlled admini-
stration 
[52] 
Mura P. et al. 1999 
cannabinoids 
Drugwipe 
 
GC/MS 
urine,saliva,tears 
Drug users and drug 
free 
[53] 
Samyn N. et al. 2000 
amphetamines,  cocaine, 
opiates, cannabis 
Drugwipe 
 
GC/MS 
saliva, plasma, urine 
Drug users 
[54] 
Pacifici R. et al. 2001 
MDMA 
Drugwipe 
 
GC/MS 
plasma, urine 
Controlled admini-
stration 
[55] 
Hazarika  P. et al. 2010 
cocaine, opiates 
Fingermark 
 
immunoassay-
Fluorescence 
microscopy 
 
Drug users 
[57] 
Fay J. et al. 1996 
metamphetamine 
PharmChek 
 
EIA-GC/MS 
 
Controlled admin-
istartion 
[58] 
Maurer HH. et al.  1997 
xenobiotics 
 
 
GC/MS-LC/MS 
blood, urine, saliva,  
hair 
General aspects on 
analytical toxicol-
ogy 
[59] 
Segura J. et al. 1998 
 
 
 
 
 
General aspects on 
analytical toxicol-
ogy 
[60] 
Kintz P. et al. 1998 
nicotine 
PharmChek 
72 hours 
GC/MS 
 
Cigarettes smokers 
and nonsmokers 
[61] 
Preston KL. et al. 1999 
cocaine 
sweat patches 
 
ELISA- GC/MS 
urine 
Clinical setting 
[62] 
Huestis M. et al. 2000 
opiates 
PharmChek 
abdomen, back/ 1 week 
ELISA- GC/MS 
urine 
Clinical setting 
[63] 
Kintz P. et al. 2002 
flunitrazepam, GHB, 
cannabinoids, LSD, 
ecstasy, ethanol 
 
 
GC/MS/MS/NICI 
 
Crime under the 
influence 
[64] 
Samyn N. et al. 2002 
cocaine, amphetamines,  
cannabis 
Drugwipe 
 
GC/MS 
blood, urine, oral 
fluid 
Roadside testing 
 
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Sweat Testing for Drugs of Abuse 
Current Medicinal Chemistry,  2013, Vol. 20, No. 4      549 
(Table 1) contd… 
Reference 
Author 
Drugs and Metabolites 
Collection Device 
Modality and Time of 
Wear 
Analytical 
Method 
Other Matrices 
Application 
[65] 
Saito T. et al. 2004 
cannabinoids 
PharmChek 
skin /12 hours 
GC/MS-NICI 
no 
Method validation, 
clinical setting 
[66] 
Follador MJ. et al. 2004 
cocaine, cocaetilene 
PharmChek 
sweating part of the 
body / 3-7 days 
GC/MS 
no 
Method validation 
[67] 
Pichini S.et al. 2005 
salvia divinorum 
 
back / 2 hours 
GC/MS 
blood, urine, saliva 
Controlled study 
[68] 
Yang W. et al. 2006 
metamphetamine, co-
caine, codeine 
skin biopsy (glu-
teus maximus) 
 
GC/MS 
no 
Clinical setting -
Method validation 
[69] 
Abanades S. et al.  2007 
GHB 
PharmChek 
back/ 6 hours 
GC/MS 
plasma, oral fluid, 
urine 
Controlled admini-
stration- Pharma-
cokinetic 
[70] 
De Martinis BS. et al.2007 
amphetamines analogs 
PharmChek 
 
GC/MS 
no 
Method validation , 
in vitro study, 
controlled admini-
stration 
[71] 
Brunet BR. et al. 2008 
methadone, heroin, 
cocaine 
PharmChek 
not specified / 7 days 
GC/MS 
 
Method validation, 
pregnancy 
[72] 
Fucci N.et al. 2008 
methadone 
PharmChek 
upper arms / 7 days 
GC/MS 
hair, urine 
Clinical setting 
[73] 
Barnes Aj. et al. 2009 
MDMA 
PharmChek 
back, abdomen / 2 hours 
- 7 days 
GC/MS 
no 
Controlled 
administration 
[74] 
Barnes AJ. et al. 2010 
methadone 
PharmChek 
back, arm / 2-24 days 
GC/MS 
no 
Controlled admini-
stration, pregnancy 
[75] 
Concheiro M. et al.  2011 
buprenorphine, metha-
done, cocaine, opiates, 
nicotine 
Band-aid 
back, upper arm, lower 
chest / 7 days 
LC/MS/MS 
no 
Method validation 
[76] 
Marchei E. et al. 2010 
methylphenidate 
PharmChek 
back/ 24 hours 
LC/MS 
oral fluid, plasma 
Pilot study 
[77] 
Cirimele V. et al. 2000 
clozapine 
 
 
LC/MS 
plasma, hair 
Schizophrenic 
patients 
[78] 
Al-dirbashi OY. et al.2001 
metamphetamine, am-
phetamine 
Abusers' clothes 
 
HPLC/ UV - 
fluorescence 
detection 
 
Method validation 
[79] 
Crouch DJ. et al. 2001 
amphetamine, cannabi-
noids, cocaine, opiates, 
PCP 
Macroduct (pilo-
carpine stimula-
tion) 
 
screening 
LC/MS/MS 
urine 
Pilot study 
[80] 
Kintz P. et al. 1998 
methadone 
PharmCheck 
upper back (72 hours) 
LC/MS 
urine 
Clinical setting 
[81] 
Samyn  N. et al. 2002 
ecstasy 
SweatWipe 
wiping with cotton over 
forehead 
GC/MS 
plasma, oral fluid, 
urine 
Controlled 
administration 
[82] 
Gallardo 2009 
 
 
 
 
 
Workplace drug 
testing 
[83] 
Marchei E. et al. 2012 
atomoxetine 
 
back / 6 hours 
LC/MS/MS 
blood, urine, oral 
fluid 
Controlled study 
[84] 
Kintz P. 1996 
opiates, cocaine, can-
nabinoids, benzodi-
azepine, amphetamine, 
buprenorphine 
PharmCheck 
5 days 
GC/MS-LC/MS 
urine 
Drug users 
[85] 
Taylor JR. et al. 1998 
methadone, cocaine, 
opiates 
PharmCheck 
5-10 days 
Immunoassay 
urine 
Clinical setting 
[86] 
Levisky JA. et al. 2001 
cocaine, metampheta-
mine 
sweat patches 
10 -14 days 
GC/MS 
urine 
Drug users 
[87] 
De la torre R. et al. 2004 
amphetamines 
 
 
 
 
Review- Pharmacoki-
netic study 
[89] 
Barnes AJ. et al. 2008 
metamphetamine, am-
phetamine 
PharmCheck 
back, abdomen / 1 week 
GC/MS 
no 
Controlled 
administration 
[90] 
Kintz P.   1997 
MBDB, BDB 
PharmCheck 
upper arm / up to 72 
hours 
GC/MS 
urine 
Controlled 
administration 
[91] 
Kintz P. et al. 1999 
ecstasy 
 
 
 
 
Review biological 
matrices 
[92] 
De Martinis BS. 2008 
amphetamines 
 
 
 
 
Review of the 
scientific literature 
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550    Current Medicinal Chemistry,  2013, Vol. 20, No. 4 
De Giovanni and Fucci 
(Table 1) contd… 
Reference 
Author 
Drugs and Metabolites 
Collection Device 
Modality and Time of 
Wear 
Analytical 
Method 
Other Matrices 
Application 
[93] 
De la torre R. et al. 2004 
cannabinoids 
 
 
 
 
Review 
[95] 
Staub  C. 1999 
cannabinoids 
 
 
 
blood, saliva, hair, 
meconium 
Review of chroma-
tographic proce-
dures 
[96] 
Kintz  P. et al. 2000 
cannabinoids 
forehead wipes 
(cosmetic pad) 
 
GC/MS 
blood, urine, oral 
fluid 
Roadside testing 
[97] 
Huestis M. et al. 2008 
cannabinoids 
PharmChek 
Chest, abdomen /1-7 
days 
GC/MS 
 
Pharmacokinetic 
study 
[98] 
Winhusen TM. et al. 2003 
cocaine 
PharmCheck 
right arm, left arm / 7 
days 
GC/MS 
urine 
Clinical setting 
[99] 
Kintz P. 1998 
codeine 
Drugwipe-
PharmCheck 
wiping forehead- upper 
arm 
GC/MS 
saliva 
Controlled admini-
stration 
[101] 
Concheiro M. et al.  2011 
buprenorphine 
PharmCheck 
12-24 hours 
GC/MS 
plasma, oral fluid 
Controlled admini-
stration in preg-
nancy 
[102] 
Balabanova S. et al. 1995 
nicotine 
pilocarpine stimu-
lation 
sweat taken every hour 
for 6 hours 
RIA/GC/MS 
 
Smokers and no 
smokers subjects 
[104] 
Marchei E. et al. 2010 
methylphenidate 
PharmChek 
up to 24 hours 
 
oral fluid 
Pediatric subjects, 
pharmacokinetic 
study 
[105] 
Lankheet N.A. et al. 2011 
sunitinib and metabolites 
PharmChek 
upper arm /24 hours 
LC/MS/MS 
no 
Method validation - 
Clinical setting 
[107] 
Samyn N. et al. 2000 
amphetamines 
 
 
on-site testing 
urine, saliva 
Roadside testing 
[108] 
Kintz P. et al. 2000 
 
 
 
 
 
Roadside testing- 
General aspects 
[109] 
Walsh JM. et al. 2004 
 
 
 
 
 
Roadside testing -
General aspects 
[110] 
Rivier L. 2000 
 
 
 
 
 
Review- Alternative 
biological samples 
[111] 
Rivier L. 2000 
 
 
 
 
 
Doping- Alternative 
biological samples 
[112] 
Huestis M.et al. 2002 
 
 
 
 
 
Review- Pregnancy 
, alternative biologi-
cal samples 
[113] 
Lozano J. et al. 2007 
 
 
 
 
 
Review- Pregnancy 
, alternative biologi-
cal samples 
[114] 
Gray T. et al. 2007 
 
 
 
 
 
Review- Pregnancy 
, alternative biologi-
cal samples 
[115] 
Daughton  CG. 2011 
 
 
 
 
 
Review- Forensic 
 
nia have been reported to be 20-50 [2]. The stratum corneum con-
tains structures that may function as diffusion shunts, thus render-
ing three potentially distinct routes of penetration through the stra-
tum corneum: hair follicles, sweat ducts and the unbroken stratum 
corneum. The study on steady state drug transport through the skin 
support the contention that bulk diffusion pathway through the in-
tact stratum corneum predominates over diffusion shunts. Delivery 
of high concentrations of the drug to the skin surface by sebum and 
sweat could produce a deposition on the stratum corneum and allow 
the skin to serve as a shallow drug depot [11, 29]. Many illicit drugs 
may diffuse through the dermal and epidermal layers of the skin 
[30]. Passive diffusion of drugs from capillaries in the skin into 
perspiration seems to be the main pathway but excretion of sub-
stances via sebum and intercellular diffusion also contribute [2, 11]. 
The mechanism appears to be linked to the concentration gradient 
in which only the free fraction of drug unbound to proteins, diffuses 
through lipid membranes from plasma to sweat. Furthermore be-
cause under normal condition sweat with a mean pH of 6.3, is more 
acidic than blood, basic drugs tend to accumulate in sweat [31]. 
Excretion into sweat depends upon a drug’s physical-chemical 
properties such as molecular mass, pKa, protein binding and lipo-
philicity. Therefore parent drugs that more easily cross membranes 
are expected to accumulate in sweat in greater concentrations than 
polar hydrophilic metabolites [11, 19, 32]. The passage of lipid-
soluble compounds from blood to other fluids is also regulated by 
the pH of the matrices considered. A modified version of the 
Henderson-Hasselbalch equation, which uses the pKa and pH, al-
lows theoretical calculation of the fluid-to-plasma concentration 
ratio [31]. There are other factors that appear not to have been con-
sidered for the transport of drugs into sweat. The rate at which 
drugs move from subcutaneous tissues to the skin surface could be 
significantly different from the rate at which drugs move from 
sweat glands to the skin surface. If the transit time for drug to move 
from subcutaneous tissue to sweat gland is considerably slower than 
time for drug to move from sweat gland to skin surface, clearance 
of the drug from the system would be significantly delayed. The 
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Sweat Testing for Drugs of Abuse 
Current Medicinal Chemistry,  2013, Vol. 20, No. 4      551 
time to transport drug from adipose tissue to the skin surface could 
be relatively short or extremely long, it depends on the rate of tran-
sition between layers, the transport mechanism, the degree of re-
versibility and the magnitude of the equilibrium constants [25].  
Cone E.J. [8] stated that the mechanism for drug entry into 
sweat was unclear, but most likely occurs by passive diffusion from 
blood to the sweat glands. An alternate mechanism could involve 
drug diffusion through the stratum corneum to the skin surface 
where drug would be dissolved in sweat. Skopp G. et al. [17] ex-
plained the passage of drug molecules from the skin capillaries into 
perspiration as a passive diffusion process governed by the same 
factors as the secretion into saliva. The elimination of a substances 
via sebum is delayed for many days as his the transcellular diffu-
sion and transport by the keratinocytes. Additionally, drug binding 
to various skin fractions [33] and reabsorption of drugs from the 
skin have been observed [34]. Therefore, a continued presence of 
drugs on the skin surface results in the time period when blood or 
urine levels are already undetectable [35]. Skopp G. et al. [17] con-
cluded that the material collected on the skin surface consists of 
various constituents and originates from various sources. The main 
analyte found on the skin surface is predominantly the parent drug. 
The time interval between drug consumption and detection on the 
skin surface depends on the nature of the particular drug and on the 
sensitivity of the analytical method used. In chronic abusers drug 
molecules are permanently present on the skin due to temporary 
reservoir of the stratum corneum [17]. 
4. ANALYTICAL METHODOLOGIES 
The usefulness of a drug test resides in its ability to accurately 
detect the presence of parent drug or metabolites in biological fluids 
or tissues following human drug administration [20]. This definition 
reflects both chemical factors that influence test outcome such as 
sensitivity, specificity and accuracy, and pharmacologic considera-
tion including dose, time and route of drug administration. Individ-
ual differences in rate of absorption, metabolism and excretion are 
also pharmacologic variables that may influence test outcome [20]. 
In the following section analytical methodologies used to detect 
drugs of abuse in sweat are reviewed; collection devices, immuno-
chemical screening tests validated for this purpose and confirma-
tory analyses are also discussed. 
a. Collection Devices 
Two different approaches in testing for drugs in sweat can be 
performed. The first method is aimed to detect recent use of drugs  
(< 24 hours) and involves only collection of sweat at a point in 
time. It is mainly oriented to identify individuals who are under the 
influence of drugs. This kind of collection device (Drugwipe) will 
be discussed in the section of screening test. The second approach 
is based on patch technology and allows monitoring of illicit drug 
use for time windows wider than those provided by urine testing. 
This is because the patches can be worn for up to one week or even 
fourteen days. Drugs accumulate in the collection device, and little 
or no drug degradation seems to occur during this time interval. 
Systematic collection of sweat specimens is difficult because of 
unequal distribution of sweat glands on different parts of the body. 
Also there is irregular production of sweat volume which is highly 
dependent upon an individual’s physical activity, emotional state, 
and the temperature of the environment [28].  
Sweating maybe induced by exercise and several milliliters of 
sweat maybe collected in conjunction with an occlusive wrapping 
or gloves. Drugs maybe caused to diffuse into the skin under an 
electrical force but this procedure has not been employed as a sam-
pling technique for diffusion of drugs out of the skin [16]. Small 
amounts of sweat maybe produced by electrical diffusion of pilo-
carpine into the skin or by warming the area; some devices have 
been developed using pilocarpine stimulation to increase sweat 
production [11, 16, 40].  
Several commercial devices are available for the collection of 
sweat for drug analysis, however the most common application is 
via the sweat patch. In recent years extraordinary advances in ana-
lytical techniques have enabled the detection of drugs and drug 
metabolites in sweat. Early patch were made of absorbent cotton 
pads sandwiched between a waterproof, polyurethane, outer layer 
and a porous inner layer that is placed against the skin. A patch was 
later developed that included a chemical binding layer in the ab-
sorbent pad to prevent external water and other molecules from 
back diffusing into the absorptive pad [8].  
Table 1 summarizes some important characteristics, such as the 
tipology of collection device, application site of the patch on human 
body, time of wearing, that are discussed in the following section. 
In 1986 the use of a sample collection device (Macroduct) of 
human sweat for anion analysis was reported [41]. Cole DE. et al. 
[41] compared concentrations of chloride and sulfate in sweat ob-
tained by use of the Macroduct capillary-coil collection device with 
results obtained by the conventional absorbent filter pad technique. 
Samples obtained with the device weighed less than those obtained 
conventionally, but sweat chloride concentrations were not signifi-
cantly different. Background contamination, a problem with the 
filter pads, was negligible with the Macroduct collector [41]. Some 
paper [2, 42] refer about the use of the patch Band-aid that consists 
of an adhesive layer on a thin transparent film of surgical dressing 
to which a rectangular absorbent pad is attached. Water, oxygen, 
carbon dioxide and other gases pass freely through the polyurethane 
adhesive “Tegaderm” covering of the patch but molecules larger 
than vapor phase isopropanol are excluded by the molecular pore 
structure of the plastic membrane. An application of Band-aid type 
collection device [43] detected cocaine and its metabolites after 
intranasal assumption, indicating that the patch technology can be 
used to diagnose a single episode of cocaine use as far back as 
seven days. A few individuals developed slight redness and irrita-
tion from the patches which were apparent upon removal.  
In 1996 a noninvasive and non-occlusive skin patch (Su-
dormed) was investigated for the systematic collection of drugs of 
abuse over a period of several days [44]. First, the applicability and 
user friendliness were tested by volunteers. A single dose experi-
ment using theophylline as a model compound showed that there 
was a delay in time before the substance could be determined in the 
pad. The so-called sweat patch appears to be a valuable tool in 
clinical and forensic toxicology, as it offers a longer and prospec-
tive surveillance period compared with blood and urine testing [44]. 
In the same year benzodiazepines and metabolites [45], codeine and 
phenobarbital [46] were analyzed from sweat collected by means of 
Sudormed. Patches were removed at specified times over one week 
and drug content was determined by gas chromatography/mass 
spectrometry. Drugs were detectable in the 2-4 hours period follow-
ing the administration.  
Huestis M.A. et al. in 1999 [11] referred about the evaluation of 
two “Fastpatch” devices in a controlled clinical trial for the disposi-
tion of cocaine, codeine and their metabolites. These patches re-
quire only 30 minutes for sweat collection because they employ 
heat-induced sweat stimulation and a larger cellulose pad for in-
creased drug collection. Through mild heating and a slightly large 
collection, “Fastpatch” [47] shows the promise of shorter required 
wear periods than other sweat patches, and possibly longer time 
periods of detected use. There were no significant differences in 
detection rates between 15, 20 and 30 minutes wear periods.  
In 1990 a device called “PharmCheck” sweat patch [11] was 
marketed as a non occlusive sweat collection, consisting of a medi-
cal-grade cellulose blotted paper collection pad covered by a thin 
layer of polyurethane and acrylate adhesives. The absorption pad 
consists of inert cellulose that retains the non volatile components 
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552    Current Medicinal Chemistry,  2013, Vol. 20, No. 4 
De Giovanni and Fucci 
of sweat collected from the surface of the skin. The release liner 
allows removal of the collection pad from the adhesive layer after 
patch use. Many advantages of the patch were observed, first of all 
it didn’t alter the transport properties of the skin and water was not 
trapped against the skin minimizing the skin irritation. Moreover 
the patch is relatively impervious to environmental contamination 
[37] and appears to be relatively tamper-proof, in fact the patch 
adhesive is specially formulated so that it can only be applied once 
and cannot be removed and successfully reapplied to the skin sur-
face [8]. The disadvantages include high inter-subject variability, 
the possibility of environmental contamination of the patch before 
the application or after removal, and the risk of accidental removal 
during a monitoring period.  
The recommended procedure is to clean the skin with 70% iso-
propanol swabbing before application of the patch [48]. Each patch 
has unique nine-digit-number printed underneath the polyurethane 
layer that is visible through a window while that patch is being 
worn, useful in maintaining the chain of custody. The water com-
ponent of sweat, vaporized by body heat, passes through the polyu-
rethane; solids, salts and drugs excreted in the sweat or that pass 
through the skin are trapped on the collection pad. Although an 
other research [4] showed that drugs can remain on the skin for 
several days after application of the patch, the 70% isopropanol is 
not the most effective solvent in removal of drugs. Drugs deposited 
on the skin of drug free volunteers several days prior the application 
of the sweat patch were not completely removed by normal hygiene 
or the cleaning procedures recommended before application of the 
sweat patch [13]. The key component of the “PharmCheck” sweat 
patch, the membrane, has been tested for the passage of externally 
applied materials. Drugs in the uncharged state rapidly penetrated 
the membrane, but charged species were greatly slowed [13]. In 
basic media detectable concentrations of cocaine, methampheta-
mine and heroin were observed at the earliest collection time after 
drugs were placed on the outside of the membrane.  
In conclusion numerous devices have been developed for col-
lection of sweat specimens. The most common device in current use 
is the “PharmCheck” sweat patch which usually is worn by an indi-
vidual for five to ten days. This device has been utilized in several 
field trials comparing sweat test results to conventional urinalysis 
and the results have been favorable. 
b. Time Window 
It was not established the optimal time of wearing sweat 
patches, although many scientists performed many studies for dif-
ferent illicit drugs. In 1998 Joseph R.E. et al. [36] established that 
after dosing some illicit drugs appeared in sebum within 1-2 hours 
and were detected for 1-2 days. A study [37] examining minimum 
length of wear necessary to detect recent or concurrent cocaine use 
in a convenience sample of active cocaine users established that the 
minimum duration that patches must be worn to detect recent or 
concurrent cocaine use is more than two hours and less than or 
equal to one day. Analyte concentrations increase significantly with 
increasing lengths of wear. The relative detection time of sweat 
respect to other specimens was suggested by Caplan Y.H. et al. 
[14]. Sweat provides a cumulative measure of drug use and could 
be applied to the monitoring of individuals in drug rehabilitation 
programs because it provides a prospective, rather than retrospec-
tive approach.  
Time window depends in part on drug use pattern [38]; in fact 
three different patterns (chronic, occasional and no-use) are readily 
identified by daily urinalysis, while patch identifies only some of 
the occasional cocaine use episodes and virtually all of the frequent 
chronic users. Some studies [31, 39] suggest that there is a time 
dependent loss of drug during patch wearing over time. One of the 
most likely mechanism involved in drug loss is re-absorption back 
into the skin. Results on 3,4-methylenedioxymethamphetamine 
(MDMA) in sweat [39] showed an inflection in the kinetic at ten 
hours post-administration. This observation revealed the possibility 
that MDMA already incorporated in patches could be reabsorbed by 
the skin. According to this notice, the re-absorption (back transfer), 
degradation or hydrolysis, and loss of cocaine to the environment 
that may account for substantial loss of cocaine from skin sweat 
collection patches during patch wear, was studied [31]. 
c. Screening Tests 
Sweat patch analysis requires extraction and sensitive chroma-
tographic methods in combination with mass spectrometry to 
achieve an effective limit of quantification. Even though, immuno-
assays commonly used to screen samples prior to confirmation by 
gas chromatography/mass spectrometry (GC/MS), and mainly 
commercialized for urine samples, were also applied to alternative 
specimens such as sweat (Table 1).  
The first immunochemical detection of drugs in apocrine sweat 
collected the samples from the axillary perspiration [49]. The de-
termination of the drugs (sum of parent drug and metabolites) was 
performed by radioimmunoassay (RIA). Measurable drug concen-
trations of cannabinoids, benzodiazepines, cocaine, barbiturates, 
morphine, methadone and cotinine were found in all samples. Bala-
banova S. et al. [40] investigated the presence of cocaine, morphine 
and methadone in sweat samples obtained after stimulation of the 
eccrine sweat glands. 
A different system [42] for the analysis of cocaine in sweat em-
ployed a solid-phase enzyme immunoassay (EIA) involving modi-
fied microtiter plates after extraction of pad with acetate buffer and 
methanol; this procedure showed to have cross-reactivity for co-
caine and benzoylecgonine with higher concentration of parent 
drug.  
In 2001 [50] two types of immunoassays (RIA and microplate 
enzyme immunoassay), were compared to detect and quantitate 
cocaine, heroin and metabolites in extracts of sweat patches. Assays 
were first evaluated for sensitivity in detection of the different con-
centrations of analytes known to be excreted in sweat. Various 
cross-reactivities were evaluated for both devices. In 2004 Moody 
D.E.et al. [51] reported a comparative analysis of sweat patches for 
cocaine and metabolites by RIA and gas chromatography-positive 
ion chemical ionization mass spectrometry. Sweat patches worn by 
subjects receiving treatment for cocaine dependence to compare the 
procedures were analyzed. Patches were extracted with acetate 
buffer pH5 directly analyzed. Time expended on performing RIA 
analysis of all the samples was cost-effective when the results were 
used to exclude negatives from and predict dilutions required for 
GC-MS analysis. RIA offers a sensitive and specific alternative 
initial test for cocaine determination in extracts of sweat patches 
[51]. 
Although the initial research in the area of alternative speci-
mens utilized RIA, newer non isotopic commercial immunoassays 
are widely available for screening of drugs and drug metabolites. 
Techniques such as Enzyme-Linked Immunosorbent Assay 
(ELISA), have been adapted for detection of analytes in sweat 
patches [14]. Kidwell D.A. et al. [38] compared three different 
immunoassays to screen specimens for cocaine on matrices not 
commonly tested: a modified manual Microgenics CEDIA, Cozart 
ELISA and OraSure ELISA. Before the immunochemical test dried 
skin swabs or patches were extracted with two portion of 0,1M of 
chloride acid. Both the Cozart and OraSure cocaine immunoassays 
performed similarly and showed a reasonably strong correlation 
with each other. In contrast, although the modified Microgenics 
assay showed the requisite sensitivity for the matrices examined, it 
had poor precision when run in a manual mode.  
A rapid onsite test called “DrugWipe” immunochemical strip 
test, was also assessed; the device is a pen size, immunochemical-
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Sweat Testing for Drugs of Abuse 
Current Medicinal Chemistry,  2013, Vol. 20, No. 4      553 
based test strip used for the detection of drugs of abuse on surface. 
The wiping part enables the user to sample drug particles from any 
kind of surface such as the skin; it is simple to use and results can 
be obtained after two minutes. In 1999 Mura P. et al. [52] evaluated 
the results of tests when applied to sweat. Regular users of cannabis 
and persons who denied consuming it were studied. The results 
obtained with DrugWipe in sweat were compared with anamnesis 
data. The Authors observed that DrugWipe may be useful for 
screening cannabis in sweat when the intake took place less than 
two hours before. Potential drug users participated voluntarily in a 
study [53] to evaluate the usefulness of the DrugWipe for the 
screening of cocaine, opiates, amphetamine and cannabinoids refer-
ring about advantages and disadvantages of the test. DrugWipe for 
the analyses of drugs of abuse in sweat [54] have also been applied 
to healthy volunteers familiar with the effects of MDMA after sin-
gle oral dose. MDMA consumption could be detected at two hours 
and for as long as twelve hours after drug administration. Pichini S. 
et al. [39] found the onsite test positive at 1.5 hours but few false-
negative results appeared in the first six hours after administration. 
A particular application [55] regarding an immunoassay based 
technique was recently used for the detection of psychoactive sub-
stances in the sweat deposited within fingermarks of a narcotic drug 
user using white light and/or a fluorescence light source. In particu-
lar Hazarika P. et al. [55] showed that morphine can be detected in 
the sweat deposited within a latent fingermark, concluding that 
fingermarks images can provide information on drug usage of an 
individual. 
d. Confirmatory Analytical Techniques 
Immunochemical screening always needs confirmatory analysis 
to be performed by chromatographic techniques. When alternative 
matrices are used the employ of confirmatory analytical techniques 
is mandatory. Advances in sensitive methodologies have enabled 
the analysis of drugs in unconventional biological materials such as 
sweat. Scientific literature refers about the detection of drugs of 
abuse in sweat employing both gas and liquid chromatographic 
methods.  
Many papers were published about the detection of xenobiotics 
in sweat (Table 1) by gas chromatography mainly coupled with 
mass spectrometry [11, 12, 25, 27, 30-32, 36, 39, 42, 45-48, 51, 53, 
56-74]. Some of them discuss sweat combined with other biological 
matrices. In this section we discuss some representative papers 
referring about the analytical procedure applied to many com-
pounds. Kintz P. et al. [12] in 1997 conducted a study on sweat 
patches applied to some subjects during heroin maintenance pro-
gram. The target drugs were extracted in acetonitrile solution and 
the residues were analyzed by gas chromatography-mass spec-
trometry in electron impact mode directly and after silylation. Her-
oin was the major drug present in sweat, followed by 6-
acetylmorphine and morphine. No correlation between the doses of 
heroin administered and the concentrations of heroin measured in 
sweat, was observed. Sweat testing for cocaine, codeine and me-
tabolites by EIA and GC/MS was performed [11] on voluntary 
people administered with cocaine and codeine. Sweat patches were 
eluted by sodium acetate buffer successively extracted by Solid 
Phase Extraction (SPE) and derivatized to obtain silyl-derivatives 
analyzed by GC/MS in selected ion monitoring mode. The authors 
concluded that the combination of EIA and GC/MS analysis was 
sensitive enough to detect cocaine in sweat after minimal abuse. 
More recently a sensitive gas chromatography-negative ion chemi-
cal ionization mass spectrometry (GC/MS-NICI) method [65] was 
developed and validated for the measurement of Delta(9)-
tetrahydrocannabinol (THC) in human sweat patches. Patches were 
extracted with methanol-sodium acetate buffer pH 5.0 for 30 min-
utes. Extracted solution was diluted with sodium acetate buffer (pH 
4.5) and extracted by solid-phase extraction columns (CleanScreen;  
 
United Chemical Technologies). Dried extracts were derivatized 
with trifluoroacetic acid and analyzed by gas chromatograph inter-
faced with an mass selective detector operated in NICI-selected ion-
monitoring mode. The same paper studied various potential inter-
fering compounds added to low quality-control samples founding to 
not influence THC quantification. Saito T. et al. [65] stated that 
GC/MS-NICI assay for THC in human sweat provides adequate 
sensitivity and performance characteristics for analyzing THC in 
sweat patches and meets the requirements of the proposed Sub-
stance Abuse and Mental Health Services Administration's guide-
lines (SAMHSA) for sweat testing [6].  
A semi-quantitative gas chromatographic/mass spectrometric 
method [66] was developed to simultaneously detect cocaine and 
cocaethylene in sweat samples collected by PharmChek, eluted with 
sodium acetate buffer (pH 5.0) and extracted by solid-phase micro-
extraction (SPME). The method showed to be very simple, rapid 
and sensitive. A positive chemical ionization gas chromatogra-
phy/mass spectrometric method was validated to simultaneously 
quantify drugs and metabolites in skin collected after controlled 
administration of methamphetamine, cocaine and codeine [68]. 
Amphetamines were eluted from PharmChek sweat patches [70] 
with sodium acetate buffer, extracted with disk solid phase extrac-
tion and analyzed using GC/MS-Electron Impact mode with a fully 
validated procedure that permitted the simultaneous analysis of 
multiple amphetamine analogs in human sweat. Another application 
for amphetamine detection in sweat patches following controlled 
MDMA administration was performed by Barnes AJ. et al. [73]. A 
sensitive, specific and validated GC/MS method (electron impact 
ionization and selected ion monitoring) was presented to simultane-
ously quantify methadone, heroin, cocaine and metabolites in sweat 
[71].  
The successful interface of liquid chromatography with mass 
spectrometry (LC-MS) has brought a new light into bioanalytical 
and forensic sciences as it allows the detection of drugs and me-
tabolites at concentrations that are difficult to analyze using the 
more commonly adopted GC/MS based techniques [75-83]. Liquid 
chromatography allows the separation of enantiomeric mixtures of 
xenobiotics employing chiral stationary phases [80]. In 1998 [80] 
an enantioselective separation of methadone was obtained using an 
alpha-1-acid glycoprotein column and liquid chromatography/Ion 
Spray Mass Spectrometry. The separation of R- and S-methadone 
can be used to document some physiologic mechanisms of excre-
tion and incorporation into sweat. The combination of LC-MS with 
innovative instrumentation such as triple quadrupoles, ion traps and 
time-of-flight mass spectrometers has been focused [82]. Methyl 
phenidate and ritanilic acid [76], buprenorphine, methadone, co-
caine, heroin, nicotine and their main metabolites [75] were deter-
mined in patches using previously validated liquid chromatography-
electrospray ionization mass spectrometric methods. A procedure 
based on LC-MS/MS was described [83] for the determination of 
atomoxetine and its metabolites in sweat and other matrices. Ana-
lytes were extracted from sweat patch with tert-butyl methyl ether 
and the organic layer was evaporated and redissolved in mobile 
phase. Separated analytes were identified and quantified by positive 
electrospray ionization tandem mass spectrometry and in multiple 
reaction monitoring acquisition mode. Kintz P. et al. [84] applied 
sweat patches to known heroin abusers coming from a detoxifica-
tion center; target drugs (opiates, cocaine, cannabinoids, benzodi-
azepines, amphetamines and buprenorphine ) were analyzed either 
by GC/MS or LC-MS depending on the target compound. de 
Oliveira C.D.R. et al. [5] published a review of chromatographic 
procedures for determination of amphetamines, cannabinoids, opi-
ates, nicotine, cocaine and alcohol in alternative biological matri-
ces. Gas chromatographic and liquid chromatographic procedures 
with different detectors and sample preparation techniques such as 
liquid/liquid, SPE and SPME extraction were discussed.  
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De Giovanni and Fucci 
5. SWEAT VERSUS OTHER MATRICES 
The selection of the specimens for drugs analysis is influenced 
by a variety of factors, principally ease of specimens collection, 
analytical and testing considerations and interpretation of results. 
Moreover each specimen gives different information respect to the 
detection window. Many papers simultaneously studied different 
biological matrices, including sweat, for the detection of drugs of 
abuse, but some of them focused on the direct comparison between 
the different specimens. The new matrices demonstrate some dis-
tinct advantages over urinalysis, e.g. less invasive procedures, dif-
ferent time course of drug detection [18]. A comparison [9] be-
tween urine, sweat and hair was performed to identify the best ma-
trix in drug testing. In contrast with urine, hair analysis has a wide 
window of detection, ranging from months to years. Testing indi-
viduals for illicit drugs with sweat patches worn continually would 
provide effective coverage for a week.  
Smith FB. et al. [3] compared the concentrations of cocaine and 
benzoylecgonine in the hair, saliva, skin secretions and urine sam-
ples of cocaine – using mothers, their children, and other adults 
living in the same environment. Most of the skin swabs from the 
adult subjects and most of their children were positive for cocaine. 
The presence of cocaine in swabs could indicate that it originated 
from sweat. However negative child urine and saliva results contra-
dict this hypothesis and imply recent surface contact. 
Joseph R.E. et al. [36] examining the disposition of cocaine, 
codeine, and metabolites in stratum corneum, sebum and plasma 
collected from African-American males after administrations of 
cocaine and codeine compared the results with the distribution in 
sweat. Stratum corneum consists of 15-20 layers of keratinized cells 
that are similar to hair with the exception that fewer disulfide bonds 
are present in stratum corneum compared with hair. Sebum is an 
oily substance composed primarily of wax ester fatty acids pro-
duced in cells of sebaceous glands. No relationship was observed 
between drug concentrations in sebum and stratum corneum com-
pared with dose. Interpretation of drug distribution and elimination 
in sebum and stratum corneum was complicated by possible con-
tamination of specimens with drugs from sweat.  
The analysis of urine and patch test for methadone, opiates and 
cocaine metabolites was performed on patients with a diagnosis of 
opiate addiction prescribed methadone [85]. There was good 
agreement between sweat patches and urine tests for methadone and 
opiates, but only moderate agreement for benzoylecgonine probably 
due to urine tests only detecting use over the last 2-3- days. Sweat 
patches may be more sensitive and detecting illicit drug use as they 
provide a longer period of collection. A comparison between urine 
and sweat patches results obtained from a woman with a history of 
chronic methamphetamine and cocaine abuse [86] was reported. 
The results of the study rise further questions about the preferential 
use of the sweat patch in detecting new episodes of drug use in 
formerly chronic drug users. Advances analytical techniques have 
enabled the detection of drugs in alternative biological specimens 
for the purposes of workplace testing. Caplan YH. et al. [14] evalu-
ated some of these specimens (oral fluid, hair and sweat) in order to 
determine their utility in Federally Regulated programs focusing the 
attention on advantages and disadvantages of the matrices consid-
ered. 
To compare the efficacy of sweat testing versus urine testing for 
detecting drug use [62] paired sweat patches were applied and re-
moved quickly and compared to 3-5 consecutive urine specimens 
from patients in a methadone maintenance treatment program. The 
identification of heroin and / or 6-acetylmorphine in sweat patches 
confirmed the use of heroin in 78% of the positive cases and differ-
entiated illicit heroin use from possible ingestion of codeine or 
opiate-containing foods. 
 
Kidwell DA. et al. [38] highlighted advantages and disadvan-
tages of daily urine and sweat patches to establish the pattern of the 
drug use among cocaine abusers. The patch identified some of the 
occasional cocaine use episodes and all of the frequent chronic 
users. A comparison [72] between hair and sweat was performed on 
heroin abusers in methadone treatment calculating the ratio between 
methadone and its metabolite in both biological matrices; these 
ratio appeared to be comparable. 
In conclusion each biological matrix shows peculiarities that 
could be used in different context hence the role of the forensic 
toxicologist is also the choice of the most suitable sample. Sweat 
samples provide cumulative measure of drug exposure, they are 
able to monitor drug intake for a period of days to weeks, they de-
tect parent drugs and metabolites, the collection is non invasive and 
the devices are relatively tamper proof. However the large variation 
in sweat production, the volume unknown and the high Intersubject 
variability are some of the major disadvantages.  
6. MONOGRAPHIC STUDIES 
In this section we summarized papers regarding the most com-
mon substances of abuse in sweat found in the international litera-
ture. 
a. Amphetamines 
Amphetamines are powerful psychostimulants, producing in-
creased alertness, wakefulness, insomnia, energy and self-
confidence in association with decreased fatigue and appetite as 
well as enhanced mood, well-being and euphoria [87]. Hepatic 
metabolism is extensive in most cases, but a significant percentage 
of the drug always remains unaltered. Amphetamine and related 
compounds are weak bases with a relatively low molecular weight 
[87]. These characteristics allow amphetamine-type stimulants to 
diffuse easily across cell membranes and lipid layers and to those 
tissues or biological substrates with a more acidic pH than blood, 
facilitating their detection in alternative matrices [87]. 
Already in the years ’80 a method for the detection of metham-
phetamine and its major metabolite in sweat from habitual users by 
mass fragmentography has been developed [88]. Sweat samples 
were extracted with methanol and after trifluoroacetyl derivatiza-
tion, analyzed by mass fragmentography. Later in 1996 [57] sweat 
was collected with the “PharmChek TM” sweat patch and drugs 
were eluted from the collection pad of the patch. A solid phase, 
enzyme immunoassay using microtiter plates was modified for 
analysis of methamphetamine. The results were confirmed by 
GC/MS. Barnes A.J. et al. [89] confirmed these results studying the 
excretion of MAMP and AMP after controlled MAMP administra-
tion. A procedure based on GC/MS [90] for the simultaneous iden-
tification of N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine 
(MBDB) and its desmethylated metabolite 3,4-(methylene dioxy-
phenyl)-2-butanamine (BDB) in sweat specimens were presented. 
Sweat specimens, which were collected by a sweat patch, were 
tested after methanolic elution. MBDB was present in higher con-
centrations than its metabolite. A review [91] of the procedures for 
the determination of MDMA derivatives, methylendioxyampheta-
mine (MDA), MDMA, methylendioxyethylamphetamine (MDEA), 
MBDB in saliva, sweat and hair was reported. The parent drug was 
found to be always in higher concentrations than metabolites. The 
development and validation of a method for the simultaneous quan-
tification of some amphetamines related drugs in sweat was also 
reported [70]. 
A brief review [92] for the detection of AMP and methylendi-
oxy-derivatives in sweat was reported. According to guidelines for 
drug monitoring using sweat as alternative specimens proposed by 
SAMHSA requirements for a positive sweat test include ampheta-
mines screen test with higher than 25 nanograms/patch and a con-
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Sweat Testing for Drugs of Abuse 
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firmation cut off of 25 nanograms/patch for amphetamines and 
methylenedioxy-derivatives. De Martinis BS [92] reviewed the 
indexed literature founding limits of detection and quantification 
ranging from 0.72 ng/patch to 5 ng/patch and from 1.4 ng/patch to 5 
ng/patch for all analytes respectively. 
Pharmacokinetic studies [81, 39] were performed after the oral 
administration of MDMA to healthy volunteers known to be recrea-
tional MDMA-users. Sweat wipes were collected after administra-
tion and the MDMA levels averaged 25 nanograms/wipe [81], also 
demonstrating large intersubject variability with peak MDMA con-
centrations for the same dose varied in magnitude 30-fold [39]. 
Recently the disposition of MDMA and metabolites in human sweat 
following controlled MDMA administration was also reported by 
Barnes A.J. et al. [73]. MDMA was the primary analyte detected 
with concentrations up to 3007 nanograms/patch. MDA was de-
tected at much lower concentrations, whereas no HMMA or HMA 
was detected. The variability in sweat excretion suggests that re-
sults should be interpreted qualitatively rather than quantitatively.  
b. Cannabis 
The use of marijuana and hashish (derived from cannabis Sa-
tiva) mostly by smoking, produces sedation, euphoria, hallucina-
tions or temporal distortion. The main psychoactive compound is 
THC which is first biotransformed to an active metabolite, 11-
hidroxy-THC which in turn is rapidly converted to an inactive me-
tabolite, 11-nor-9-carboxy-THC [8]. In contrast to the majority of 
drugs of abuse which are weak base and tend to concentrate in bio-
logical matrices more acidic than plasma, THC is a neutral mole-
cule and its diffusion is expected to be slower [93]. Not surprisingly 
lipophilic drugs can be detected in skin and adipose tissue. Johans-
son E. [94] demonstrated that in heavy marijuana users, THC re-
mained in adipose tissue up to 28 days after smoking. Only a few 
papers were found in literature referring about the detection of can-
nabis in sweat. Early paper detecting THC in sweat [49] found the 
parent drug to be the primary analyte. In a study conducted in a 
detoxification center, sweat patches were applied to 20 known her-
oin abusers. Target drugs analyzed either by GC-MS or LC-MS 
included delta9-tetrahydrocannabinol, identified in nine cases (4-38 
ng/patch) [84]. In 1999 Staub C. [95] found THC in low amount 
and the principal acidic urinary metabolite (11-nor-9-carboxy-THC) 
has been never detected in sweat. An editorial discussion on the 
usefulness of sweat testing of the detection of cannabis smoke has 
been reported in 2004 [93]. In order to demonstrate an intake of 
cannabis Mura P. et al. [52] evaluated the results of DrugWipe. 
Regular users of cannabis and persons who denied consuming it 
were studied. The results obtained were compared with anamnesis 
data and indicated that DrugWipe could be useful for screening 
cannabis in sweat when the intake took place less than two hours 
before. The non-instrumental immunoassay Drugwipe was also 
used in a Belgian study for the screening of cocaine, opiates, am-
phetamine and cannabinoids in saliva and sweat [53]. Procedures 
using GC/MS to test for THC in forehead wipes were developed 
and validated [96, 65]. Injured drivers were tested, some of them 
were positive for THC, but metabolites were never detected [96]. 
Saito T. et al. [65] developed an assay with adequate sensitivity and 
performance characteristics for analyzing THC in sweat patches 
meeting the requirements of the proposed SAMHSA’s guidelines 
for sweat testing [6]. Huestis MA. et al. [97] evaluated THC excre-
tion in daily cannabis users after cessation of drug use. Moreover 
some subjects were administered oral doses of THC for five con-
secutive days; the results demonstrated that THC does not readily 
enter sweat following oral ingestion.  
c. Cocaine 
Cocaine is a powerful addictive stimulant drug extracted from 
“Erythroxylon coca” leaves that can be administered intranasally, or 
by intravenous or intramuscular injection. It can also be taken 
orally, sublingually, vaginally or rectally or it can be smoked. The 
human metabolism transforms cocaine into two major metabolites 
(benzoylecgonine and ecgonine methylester) and some other minor 
metabolites [8]. In recent years cocaine is becoming the most popu-
lar drug of abuse and many studies on its detection in sweat have 
been published.  
A clinical study [43] examined a skin patch method of monitor-
ing drug use after two different treatment doses. Analysis of the 
patch content yielded cocaine levels from the cocaine subjects that 
accurately reflected usage. Mean levels were significantly different 
for the two treatment doses. The data do indicate that the patch 
technology can be used to diagnose a single episode of cocaine use 
as far back as seven days. 
The use of a sweat patch for detecting cocaine abuse in cocaine-
dependent patients participating in a clinical trial was studied [98]. 
The reliability and validity of quantitative sweat patch results, the 
possible degradation of cocaine to benzoylecgonine as a function of 
the length of time that a patch is worn and the relative costs associ-
ated with sweat patch were also evaluated. The results revealed no 
significant degradation of cocaine to benzoylecgonine associated 
with wearing the patch. The excretion of cocaine in sweat of volun-
teers receiving low and high doses, was again evaluated in 2005 
[30]. Pharm-Chek sweat patches were collected before the admini-
stration, during and after controlled dose. Cocaine was the primary 
analyte detected and frequently the only one. 
Some contamination studies were performed on different popu-
lation. An application of sweat test was performed on cocaine-using 
mothers and their children [3]. To distinguish actual drug use from 
passive exposure to the drug a comparison between forehead swabs 
and other biological materials were performed. In a second trial a 
random population of adults at a major United States University [4] 
was studied. Sweat was obtained by wiping the forehead with a 
cosmetic puff containing isopropanol. Moderate amounts of cocaine 
and benzoylecgonine are slowly lost when placed on the skin possi-
bly due to absorption. To test the persistence of larger amounts of 
cocaine and benzoylecgonine on the skin through removal by nor-
mal hygiene and absorption by the body, two sets of experiments 
were carried out. After three days of normal hygiene and three re-
moval steps the drugs were undetectable.  
More recently Kidwell D.A. et al. [38] made a comparison of 
daily urine, sweat and skin swabs among cocaine users. Large 
quantities of cocaine were found on the skin of individuals with 
urine positivity and an evaluation of drug contamination on the 
external patch membrane was performed. Immunoassays were stud-
ied and validated in various papers using different techniques. A 
solid-phase enzyme immunoassay [42] involving microtiter plates 
was modified for the analysis of cocaine in sweat, collected with 
the PharmChek patch that contained primarily parent cocaine, and 
the method was validated for qualitative detection.  
The monitoring of cocaine use was performed in substance-
abuse-treatment patients by sweat testing [61]. Sweat and urine 
specimens were collected from methadone-maintenance patients to 
evaluate the use of sweat testing to monitor cocaine use through 
ELISA test. Immunoassays were also evaluated by Moody D.E. et 
al. [50] for their ability in the detection of cocaine and metabolites 
discussing the cross reactivity. Later a RIA method [51] using 
sweat patches worn by subjects receiving treatment for cocaine 
dependence was developed. 
Various methodologies were proposed to identify and quantitate 
cocaine and its metabolites. A semi-quantitative method (SPME 
followed by GC/MS) was elaborated to simultaneously detect co-
caine and cocaethylene in sweat [66]. GC/MS [68, 71] and LC-MS 
methods [75] for many substances including cocaine and its me-
tabolites in sweat were developed and comprehensively validated. 
These methods permit fast and simultaneous quantification of many 
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556    Current Medicinal Chemistry,  2013, Vol. 20, No. 4 
De Giovanni and Fucci 
drugs and metabolites in sweat patches, with good selectivity and 
sensitivity. 
The minimum length of wear necessary to detect recent or con-
current cocaine use in a convenience sample of active cocaine users 
was examined [37]. Differences in analyte concentrations with in-
creasing longer-term wear were observed. Some studies compared 
different sites of application of the patches to establish the best 
collection point. Huestis M.A. et al. [11] reviewed sweat testing for 
cocaine discussing that diversifying the site of collection change 
drug disposition in sweat. Generally concentration of cocaine are 
higher in sweat specimens collected on the hand respect to the 
torso. This observation is likely to be due to differences in the anat-
omy and physiology of the skin on the palm of the hand compared 
to the torso skin. Uemura N. et al. in 2004 [31] also investigated the 
effect of sweat patch location (back and shoulder) on cocaine levels 
after controlled intravenous cocaine exposure in different subjects. 
The analysis showed cocaine and metabolites levels in sweat eight-
fold higher on the back than those on the shoulders.  
A continuing social problem is presented by the large number 
of individuals who smoke crack; crack is a mixture of cocaine hy-
drochloride and sodium hydrogen carbonate which liberates the 
cocaine base from the hydrochloride with some cracking noise. 
Liberty HJ et al. [47] have identified unique pyrolysis products of 
crack or burned cocaine as anhydroecgonine methylester and 
ecgonidine through GC/MS that allow for the detection of crack use 
distinct from other cocaine use.  
d. Opiates 
Opium is a natural product containing morphine as the principal 
alkaloid. Illicit market synthesizes heroin adding two acetyl groups 
to morphine in order to obtain a stronger drug. Following intake, 
heroin is rapidly deacetylated to 6-acetylmorphine which is then 
further hydrolyzed to morphine at a slower rate [8].  
Many papers refer that opiates are excreted in sweat, and the 
parent drug is the predominate analyte found. Heroin and its me-
tabolites [2] were investigated in sweat patches in order to evaluate 
the possible use of alternative matrices. The data suggested that 
sweat patches could serve as a useful monitoring device in surveil-
lance of individuals in treatment and probation programs. In a study 
conducted in a detoxification center [84], sweat patches were ap-
plied to known heroin abusers, to detect heroin, 6-acetylmorphine, 
morphine and codeine. When detected, heroin was always present 
in lower concentrations than 6-acetylmorphine, which was the ma-
jor analyte found in sweat. It is noteworthy that sweat is one of the 
few matrices in which heroin is readily detected. After opiate (co-
deine, or heroin or poppy seeds) administration [48] patch perform-
ances were evaluated. Heroin and 6-acetylmorphine or codeine but 
little morphine were found in sweat after heroin or codeine admini-
stration as contrasted to the metabolite profile found in urine or 
blood. Heroin and 6-acetylmorphine or codeine appear in sweat 
within 24 hours of administration of opiates in controlled studies 
and peak within the first three days. An other study [12] conducted 
during an heroin maintenance program applied sweat patches to 
subjects that received intravenously two or three doses of heroin 
hydrochloride ranging from 80 to 1000 mg/day. The sweat patch 
was applied ten minutes before the first dosage and removed ap-
proximately 24 hours later, minutes before the next dosage. Except 
in one case, heroin was the major drug present in sweat, followed 
by 6-acetylmorphine and morphine. No correlation between the 
doses of heroin administered and the concentrations of heroin 
measured in sweat were observed. 
The time course, the cumulative excretion, the intra-subject 
variability, the influence of site application, and the concentrations 
of codeine in sweat following administration of a single dose of the 
drug, was also performed [46]. Codeine was detectable at one hour 
following the administration, and a plateau concentration was ob-
served on the third day. The peak codeine concentration was deter-
mined during the 12-24 hours period. Morphine was never detected 
in sweat and inter-subject variability was enormous, but Kintz P. et 
al. [46] suggest that the sweat patch technology can be useful for 
documenting drug use over a one week period of surveillance. Co-
deine phosphate was orally administered to six subjects testing 
sweat immediately with the Drugwipe and applying the sweat patch 
at the same time [99]. Codeine was quantified in the patch by 
GC/MS. In all subjects except one, the Drugwipe tested positive for 
opiates. After controlled oral codeine administration [32, 68] sig-
nificant variability in concentrations was observed in patches ap-
plied to various locations in the upper body. Codeine was detected 
within one hour and peaked within 24 hours and no metabolites 
were detected. The study comprehensively evaluated hourly and 
weekly sweat patches to characterize the duration, accumulation, 
reproducibility, time of first appearance and dose concentration 
relationship of codeine excretion in sweat. 
Methadone is a opioid pain reliever, similar to morphine. It re-
duces withdrawal symptoms in people addicted to heroin or other 
narcotic drugs without causing the "high" associated with the drug 
addiction. It is used in detoxification and maintenance programs for 
the management of physical dependence of narcotics [1]. Some 
studies were found in literature about its possible detection on 
sweat samples. Henderson G.L. et al. [56] already in 1973 referred 
about the excretion of methadone and metabolites in human sweat. 
Later [44, 80, 85, 100] the presence of methadone was again inves-
tigated in 24 hours perspiration samples obtained from patients 
receiving daily maintenance doses of the drug. No correlation be-
tween the dose methadone administered and the concentrations of 
methadone in sweat was observed but sweat patches were reliable 
giving valid results for patient on maintenance methadone.  
The authors of the present review didn’t find papers referring 
the detection of methadone in sweat in the scientific literature in the 
period 1998 – 2007. Successively [72] a comparison between hair 
and sweat samples from patients in long term maintenance therapy 
was performed. Fucci N. et al. [72] referred about their experience 
with sweat applied to supervise methadone therapy of heroin abus-
ers. Some advantages respect to hair were found such the time win-
dow of sweat shorter than hair that allows the doctor easily to check 
the therapeutic program of abusers. A good agreement between 
patients, when the application of the patch was proposed instead of 
the daily collection of urine or hair cut, was underlined. The devel-
opment of an analytical method for the simultaneous quantification 
of methadone and other xenobiotics in sweat is reported by Brunet 
B.R. et al. [71]. The excretion of methadone in sweat of pregnant 
women after controlled methadone administration was also studied 
[74]. Methadone was present in all weekly patches, correlation 
between patch concentrations and total amount of drug adminis-
tered and concentrations and duration of patch wear were both 
weak. 
Buprenorphine is a strong opioid painkiller which is used to 
treat moderate to severe pain; it is currently under investigation as a 
pharmacotherapy to treat abusers for opioid dependence [1]. Some 
papers [26, 101] evaluated the utility of sweat testing for monitor-
ing of drug use in outpatient clinical settings and opioid dependent 
pregnant women. Chawarski M.C. et al. [26] compared sweat toxi-
cology with urine toxicology and self report drug use during a ran-
domized clinical trial of the efficacy of buprenorphine for treatment 
of opioid dependence in primary care settings. The other research 
[101] evaluated buprenorphine and its metabolites pharmacokinet-
ics after sublingual administration to pregnant women, suggesting 
that, like methadone, upward dose adjustments may be needed with 
advancing gestation.  
e. Other Substances 
Other substances were investigated in human sweat, such as 
nicotine, the object of some scientific studies before the year 2000. 
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Current Medicinal Chemistry,  2013, Vol. 20, No. 4      557 
In 1990 [49] specimens of apocrine and eccrine sweat collected 
without and after pilocarpine stimulation from smokers and non-
smokers exposed to tobacco smoke were investigated. The concen-
trations were determined by RIA, so that the values obtained repre-
sent the concentrations of nicotine plus its metabolites, e.g. cotin-
ine. The levels measured in apocrine sweat were higher than those 
in eccrine sweat. The presence of nicotine in sweat obtained from 
smokers and non-smoker exposed to tobacco smoke after four hours 
to eight days of nicotine-free time was investigated [102]. The sum 
of nicotine and its metabolites were determined by RIA. The pres-
ence of unchanged nicotine was revealed by GC/MS. In a study 
conducted with cigarettes smokers and nonsmokers [60], Pharm-
Chek sweat patches were applied to subjects for 72 hours. Nicotine 
was determined using GC/MS, and it was not detected in non-
exposed nonsmokers, while it was found in passive and active 
smokers. 
Not only narcotics and stimulants, but also many alkaloids and 
barbiturates are excreted in the sweat and detected quantitatively by 
the same principles [46, 103]. To determine the time course, the 
cumulative excretion, the intra-subject variability, the influence of 
site application, and the concentrations of phenobarbital in sweat 
following administration of a single dose of the drug a clinical 
study was performed [46]. Phenobarbital was first observed three 
hours after administration, and cumulative excretion was continual 
throughout the week. Intersubject variability was enormous with the 
concentrations in the range of 0.5 - 33 nanograms/patch. These data 
suggest that the sweat patch technology can be useful for docu-
menting drug use over a one-week period of surveillance. 
Benzodiazepines were also studied [45] to determine the cumu-
lative excretion, the time course, the dose-concentration relation-
ship, and concentrations of diazepam and its metabolites in sweat 
following oral administration of single dose of the drug. Irrespec-
tive of the time of collection, diazepam and nordiazepam were pre-
sent, but oxazepam was never detected. Drugs were detectable in 
the two to four hours period following the administration. Concen-
trations were in the range 0.1 to 6.0 nanograms/patch for both 
drugs.  
The determination of clozapine in sweat was performed using a 
liquid chromatographic method [77]. The correlation between clo-
zapine levels in hair and sweat and the daily dose was also studied. 
The main active ingredient of the hallucinogenic mint Salvia Divi-
norum (Salvinorin A) was also investigated in sweat but never de-
tected from consumers [67]. After controlled administration of 
gamma-hydroxybutyric acid (GHB) sweat and other biological 
fluids were analyzed by GC/MS [69]. GHB was detected in sweat 
at low concentrations, hence this biological matrix appears not to be 
suitable for monitoring GHB consumption. Methylphenidate, a 
prescription amphetamine derivative used in the treatment of atten-
tion-deficit hyperactivity disorder, has been amply described in 
conventional biological matrices. Recently, the excretion of meth-
ylphenidate and its principal metabolite (ritalinic acid ) in sweat has 
been studied [76, 104]. Atomoxetine, a drug approved for the 
treatment of attention–deficit hyperactivity disorder, was recently 
detected by a LC-MS/MS procedure in conventional and non-
conventional biological matrices from individuals in drug treatment 
[83]. Sunitinib, used to treat tumors such as gastrointestinal, renal 
cell carcinoma, pancreatic neuroendocrine tumors, was detected in 
sweat collected from a patient therapeutically treated with the drug 
[105]. 
7. FORENSIC APPLICATIONS 
Sweat testing received particular attention by scientists for its 
possible application on roadside and workplace drug testing that 
would be the object of the following sections.  
a. Roadside Drug Testing 
To establish driver’s impairment sweat samples are obtained by 
wiping the forehead. Some studies were found in literature referring 
experiences in this context.  
An interesting European study called “ROSITA” (ROadSIde 
Testing Assessment) was born to evaluate devices for the analysis 
of sweat and other matrices in order to control drivers under the 
influence of drugs (www.rosita.org). The objective of the ROSITA 
study is “to identify the requirements for road side testing equip-
ment, and to make an international comparative assessment of ex-
isting equipment or prototypes. The assessment will address road 
side testing result validity, equipment reliability, usability and us-
age costs”. 
The first results published [106, 107] referred about the evalua-
tion of various analytical devices to test sweat. Eight nations were 
enrolled and about 3000 drivers were tested to evaluate the role 
played by the drugs of abuse in the drive performances. The useful-
ness of sweat was demonstrated, it was best accepted respect to 
other matrices by drivers, but the need to more investigation was 
underlined [17].  
Prospective analytical studies [96, 108] were performed in large 
population of drivers implicated in non-fatal traffic accidents to 
determine the significance of drug levels observed in blood, urine, 
saliva and sweat. The samples were tested for pharmaceuticals and 
drugs of abuse by hyphenated chromatographic methods. The 
authors observed that a limitation in the use of the sweat for road-
side testing is the absence of a suitable immunoassay to detect the 
parent compound. Sweat samples by wiping the forehead were 
obtained from drivers who failed the field sobriety tests at police 
roadblocks [64]. The positive predictive value of sweat wipe analy-
sis by GC/MS was over 90% for cocaine and amphetamines and 
80% for cannabis.  
A global overview [109] on the issue of drugs and driving dis-
cussing the utility of alternative specimens including sweat was 
presented by Walsh J.M. et al. in the year 2004. A special attention 
for the effects of medicinal and illegal drugs on driving perform-
ance was reported and Walsh J.M. et al. drew conclusion regarding 
the risk of the drug to traffic safety. 
b. Workplace Drug Testing 
Workplace drug testing is a well-established application of fo-
rensic toxicology and it aims to reduce workplace accidents caused 
by affected workers. Several classes of abused substances may be 
involved, such as alcohol, amphetamines, cannabis, cocaine, opiates 
and also prescription drugs, such as benzodiazepines. Since the 
1970’s, urine drug testing has been the most common technique for 
detecting drug use in the workplace.  
National laws of each country provide the underpinnings of 
drug-testing programs, but most countries have not addressed use of 
these alternate matrices. In 2001 [18] Cone EJ. reviewed national 
and local laws of many countries providing the employ of drug-
testing programs, discussing that only a few countries have statutes 
that specifically mention the use of alternate biological matrices. In 
our knowledge only very few advances have been made in the last 
ten years. Caplan Y.H. et al. [14] discussed about the use of alterna-
tive specimens for workplace drug testing suggesting that oral fluid, 
hair and sweat appear to sufficiently meet the requirements to be 
added. No other paper were found in the recent literature. On 13th 
April 2004 the U.S. Department of Health and human services 
(www.samhsa.gov) published a notice in the Federal Register pro-
posing to establish also scientific and technical guidelines for the 
testing of alternative matrices (like sweat) in addition to urine 
specimens [6].  
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c. Other Forensic Applications 
Forensic toxicology can be involved in several situations to 
document impairment, such as: crime under influence, date rape, 
psychiatric disorders, determination of the cause of death. In some 
particular situations, it can be very cautious to investigate exposure 
to psycho-active drugs, due to late sampling of biological speci-
mens. 
In the context of the “crime under the influence” many biologi-
cal specimens have been tested to verify the use of drugs after sex-
ual assaults such as drugs spiked in food. Only a paper was found 
[63] exploiting the use of sweat to detect drugs administered during 
sexual assault.  
The use of sweat in doping context was referred [59] to detect 
anabolic steroids, diuretics and corticosteroids. Two papers regard-
ing the possible application of sweat in sport doping were published 
[110, 111] that discussed sampling, analytical procedures and inter-
pretation of the results. 
Being the skin constantly exposed to sweat and sebum, drugs 
may be sequestered in this tissue. Moreover there is evidence that 
after chronic exposure lipophilic drugs may be stored in adipose 
tissue creating a drug depot. Hence in this section we consider some 
paper describing the analysis of drugs in these matrices. Yang W. et 
al. [68] described the analysis of 55 skin biopsies collected from 15 
volunteers after controlled administration of methamphetamine, 
cocaine and codeine. Levisky J.A. [25] considered the adipose tis-
sue and skin in illicit drug related deaths for qualitative and quanti-
tative analyses removing the tissues from the abdominal region 
during the autopsy. 
Particular applications detected methamphetamine in garments 
belonging to known-abusers [78] extracting the drugs from the 
textile using a mixture of organic solvents and morphine in the 
sweat deposited within fingermarks of a narcotic drug user [55]. 
8. DRUG USE DURING PREGNANCY 
The maternal abuse is often underestimated due to the stigma of 
drug use during pregnancy and the accompanying legal, ethical and 
economic issues. In utero drug exposure can have a severe impact 
not only on the development of the fetus, but also on the child dur-
ing later stages of life. Accurate identification of in utero drug ex-
posure has important implications for the care of the mother and 
child, but can raise difficult legal issues. Detection of in utero drug 
exposure has traditionally been accomplished through urine testing; 
however, the window of detection is short, reflecting drug use for 
only a few days before delivery, hence other biological matrices 
such as sweat can be used [112]. Maternal drug use during preg-
nancy can be monitored with alternative matrices such as sweat 
testing that offers a longer window of detection of about one week 
and decreases the likelihood of missing recent use.  
Some reviews regarding various biological matrices [113] and 
bioanalytical methods [114] useful for the detection of exposure 
from different gestational periods in pregnancy to drugs of abuse 
were found in literature. Drug detection in maternal blood, oral 
fluid, and sweat accounts only for acute consumption that occurred 
in the hours previous to collection and gives poor information con-
cerning fetal exposure [113]. 
Some characteristics of sweat such as the easy and noninvasive 
collection, the detection window of a few days before a patch appli-
cation and the difficult to quantify the amount of sweat secreted 
allow this matrix to be considered for qualitative purposes [114]. 
Sweat specimens from pregnant opioid – dependent women (treated 
with methadone) were examined to detect methadone, cocaine and 
heroin metabolites [27, 74]. Correlation between patch concentra-
tions and total amount of methadone administered and concentra-
tions and duration of patch wear were both weak. Although there 
were large intra- and inter-subject variations in sweat drug concen-
trations, sweat testing was an effective alternative technique to 
qualitatively monitor illicit drug use and simultaneously document 
methadone medication-assisted treatment [27]. An opioid-depen 
dent buprenorphine-maintained pregnant woman [75] was submit-
ted to weekly sweat patches application detecting buprenorphine, 
cocaine, opiates, methadone and tobacco biomarkers with good 
selectivity and sensitivity. 75.0% of sweat patches were positive for 
buprenorphine, 93.8% for cocaine, 37.5% for opiates, 6.3% for 
methadone and all for tobacco biomarkers. The pharmacokinetics of 
buprenorphine was studied [101] after high-dose sublingual tablet 
administration in three opioid-dependent pregnant women detecting 
buprenorphine and its metabolite in only four of 25 specimens in 
low concentrations (less than 2.4 ng/patch). 
9. INTERPRETATION OF THE ANALYTICAL RESULTS 
Duration of patch wear, variability in sweat production, and 
stability of drugs on the patch are some of the complex factors in-
volved in interpretation of drug concentrations in this specimen. A 
major limitation of sweat patch testing [79] is that the production of 
liquid perspiration varies with ambient temperature and physical 
activity. Therefore the volume of perspiration collected by the patch 
worn during the week, is unknown. This precludes meaningful 
quantitative analysis of drugs detected on the patch and limits the 
interpretative value of a sweat patch drug test result. Moreover 
being the volume of sweat limited, preserving part of the specimen 
for an independent retest is difficult. 
Despite of this consideration, SAMHSA issued mandatory 
guidelines [6] for the federal workplace drug testing programs for 
sweat testing. After chronic exposure lipophilic drugs may be 
stored in adipose tissue hence they do accumulate in fat falsely 
suggesting new episodes of drug intake. Interpretation of drug dis-
tribution and elimination in sebum and stratum corneum is compli-
cated by possible contamination of specimens with drugs from 
sweat [2, 36], particularly because parent drug is often detected as 
the major analyte in the sweat patch.  
Cone EJ. et al. [2] refer that during the course of the cocaine 
experiments, sweat patches were challenged in passive drug con-
tamination studies (transdermal and cocaine vapor). The exterior 
environment during exposure was ruled out as an alternate explana-
tion because the same subject showed negative results in other ex-
periments. The authors concluded that environmental contamination 
of the sweat patch had most likely occurred during the removal and 
the storage process resulting in positive tests for cocaine. Obviously 
careful procedures must be employed in removal and handling of 
the sweat patches to prevent the production of false positive drug 
test results. 
False positive interpretations may arise from prior presence of 
drugs on the exterior of the skin which are not removed by the 
cleaning process. Skin contamination experiments is distinct from 
drugs permeating the skin, entering the blood stream and being re-
excreted by the sweat into the patch [13]. The presence of contami-
nants in the environment and hence the importance of the correct 
forensic interpretation was recently underlined by Daughton C.G. in 
2011 [115]. Many drugs, especially illicit drugs, are readily ex-
creted via sweat glands, including those on the fingers. This has the 
potential to result in contamination of samples during their collec-
tion or during various steps in analysis. Contamination of samples 
by analysts who are using prescribed or illicit drugs is an under-
investigated potential source of erroneous data.  
The presence of metabolites in sweat is thought to distinguish 
passive exposure from active use. The finding in skin wipes of 
unique metabolites of drugs that are not present in the environment 
would indicate use rather than exposure. The presence of heroin, 6- 
acetylmorphine, acetylcodeine allows unequivocal differentiation 
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Sweat Testing for Drugs of Abuse 
Current Medicinal Chemistry,  2013, Vol. 20, No. 4      559 
between licit opiate use and heroin abuse [27]. The presence of 
cocaethylene or ecgonine methylester is thought to indicate the use 
of cocaine rather than exposure to it [16]. This unique metabolites 
are present in minor amounts requiring very sensitive techniques for 
detecting use versus exposure. Kidwell DA. et al. [16] stated that 
the benzoylecgonine/cocaine ratio varies widely. They also ob-
served that some subjects showed a very high ratio, they speculated 
the presence of active enzymes on their skin or different excretory 
pathways for cocaine and its metabolites. However they performed 
experiments that showed cocaine stable in contact with the skin. 
This implies that the enzymes are not sufficiently active for sub-
stantial cocaine hydrolysis [16].  
Kidwell DA. et al. [38] found positive results for an unknown 
period after cocaine cessation. In a legal setting the issue of when 
drug use occurs is crucial. For example, judges require drug absti-
nence as a standard condition of probationary release. Prior drug 
use may be irrelevant to meeting this condition. If the sweat patch is 
used as a stand-alone test for determining drug use status during the 
period that the sweat patch is worn, then it is essential that the patch 
does not falsely report previous drug use as “current drug use”. For 
chronic users it is not clear whether a cocaine appearing in the 
patches came from current drug ingestion, previous drug ingestion, 
previous drug contamination, current drug contamination, or a 
combination of the above.  
CONCLUSIONS 
Forensic scientists have long detected the presence of drugs in 
biological materials using body fluids such as urine, blood, and/or 
tissues. In recent years, remarkable advances in sensitive analytical 
techniques have prompted the analysis of drugs in unconventional 
biological samples more easily collectable. 
Patch technology allows the monitoring of illicit drug use for 
time windows wider than those provided by urine testing. Because 
the patches can be worn for up to one week, drugs tend to accumu-
late in the collection device, and no drug degradation appears to 
occur during this time interval. A series of clinical studies were 
designed to determine the identity, concentration, time course, dose 
dependency, and variability of drug and metabolite excretion in 
sweat following administration of single dose of illicit drugs to 
human subjects. 
Although there are large intra- and inter-subject variations in 
sweat drug concentrations, sweat testing was found to be an effec-
tive alternative technique to qualitatively monitor illicit drug use 
and simultaneously document medication-assisted treatment. 
Advantages of sweat analysis using sweat patches include: con-
tinuous drug testing can be undertaken over a longer period (up to 
7-14 days) than urine or saliva, the process of specimens collection 
is less invasive than urine collection, the patches appear to be rela-
tively tamper resistant and tamper evident, and the patch can be 
applied and removed quickly and little training is required for the 
sanitary. Moreover sweat patches are readily accepted by subjects 
limiting the number of required monitoring visits. 
Disadvantages of sweat analysis using sweat patches limited 
routine use of this biological matrix. Concentrations of drugs in the 
patch are much lower than urine, making repeated testing (confir-
mation retesting) a potential problem. Possibility of environmental 
contamination of patch before application or after removal must be 
taken into account. Moreover there is the risk of accidental or de-
liberate removal of patch during monitoring period. The effects of 
vigorous or prolonged exercise on the transfer of drugs into sweat 
and / or the deposition of these drugs onto the patch are unknown 
and there is evidence that outward transdermal migration of some 
accumulated drugs may lead to an incorrect interpretation of new 
drug use. Finally the possibility of time-dependent drug loss from 
the patch by drug degradation on skin is also possible together with 
re-absorption into the skin and consequent volatile losses through 
the covering membrane of the patch.  
Sweat patches provide a convenient alternative that avoids 
some of the problems with drug testing such as violations of pri-
vacy in observed urination, possibility of disease transmission, and 
transport of noxious fluids. This technology benefits from low inva-
siveness and pose fewer ethical problems for sample collection than 
does blood or urine testing. Nevertheless it would be premature to 
replace urine toxicology testing with sweat patch in both research 
and clinical settings. Continuing improvements in sweat collection 
and testing methods may result in the availability of a substantially 
improved sweat device in the near future. 
CONFLICT OF INTEREST 
The author(s) confirm that this article content has no conflicts 
of interest. 
Declared none. 
REFERENCES 
[1] 
Hardman J.G.; Limbird L.E.; Molinoff P.B.; Ruddon R.W.; Goodman Gil-
man A.; Goodman & Gilman: Le basi farmacologiche della terapia. 
McGraw-Hill Ed. Milano, Italy. 
[2] 
Cone, E.J.; Hillsgrove, M.J.; Jenkins, A.J.; Keenan, R.M.; Darwin, W.D. 
Sweat testing for heroin, cocaine, and metabolites. J Anal Toxicol. 1994, 18, 
298-305. 
[3] 
Smith, F.P.; Kidwell, D.A. Cocaine in hair, saliva skin swabs and urine of 
cocaine users’ children. Forensic Sci. Int. 1996, 83, 179-189. 
[4] 
Kidwell, D.A.; Blanco, M.A.; Smith, F.P. Cocaine detection in a university 
population by hair analysis and skin swab testing. Forensic Sci. Int. 1997, 84, 
75-86. 
[5] 
de Oliveira, C.D.R.; Roehsig, M.; de Almeida, R.M.; Rocha, W.L.; Yo-
namine, M. Recent advances in chromatographic methods to detect drugs of 
abuse in alternative biological matrices. Current Pharmaceutical Analysis 
2007, 3(2), 95-109. 
[6] 
Bush, D.M. The US mandatory guidelines for federal workplace drug testing 
programs: current status and future considerations Forensic Sci. Int. 2008, 
174, 111-119. 
[7] 
Vearrier, D.; Curtis, J.A.; Greenberg, M.I. Biological testing for drugs of 
abuse. EXS 2010, 100, 489-517. 
[8] 
Cone, E.J. New developments in biological measures of drug prevalence. 
NIDA Res Monogr. 1997,167, 108-29. 
[9] 
Kintz, P. Drug testing in addicts: a comparison between urine, sweat, and 
hair. Ther. Drug Monit. 1996, 18, 450-5. 
[10] 
Phillips, M. An Improved Adhesive Patch for Long-Term Collection of 
Sweat. Biomat. Med. Dev. Art. Org. 1980, 8(1), 13-21. 
[11] 
Huestis, M.A.; Oyler, J.M.; Cone, E.J.; Wstadik, A.T.; Schoendorfer, D.; 
Joseph, R.E. Jr. Sweat testing for cocaine, codeine and metabolites by gas 
chromatography-mass spectrometry. J. Chromatogr. B Biomed Sci. Appl. 
1999, 733, 247-64. 
[12] 
Kintz, P.; Brenneisen, R.; Bundeli, P.; Mangin, P. Sweat testing for heroin 
and metabolites in a heroin maintenance program. Clin Chem. 1997, 43(5), 
736-9. 
[13] 
Kidwell, D.A.; Smith, F.P. Susceptibility of PharmChek drugs of abuse patch 
to environmental contamination. Forensic Sci. Int. 2001,116 (2-3), 89-106. 
[14] 
Caplan, Y.H.; Gooldberger, B.A. Alternative specimens for Workplace Drug 
Testing. J. Anal. Toxicol. 2001, 25, 396-9. 
[15] 
Inoue, T.; Seta, S. Analysis of Drugs in Unconventional Samples. For. Sci. 
Rev. 1992,4,89–107. 
[16] 
Kidwell, D.A.; Holland, J.C.; Athanaselis, S. Testing for drugs of abuse in 
saliva and sweat-review. J. Chromatogr. 1998, 713, 111-135. 
[17] 
Skopp, G.; Pötsch, L. Perspiration versus saliva--basic aspects concerning 
their use in roadside drug testing.. Int. J. Legal Med. 1999, 112(4), 213-21. 
[18] 
Cone, E.J. Legal, workplace, and treatment drug testing with alternate bio-
logical matrices on a global scale. For. Sci. Int. 2001, 121(1-2)7-15. 
[19] 
Dolan, K.; Rouen, D.; Kimber, J. An overview of the use of urine, hair, sweat 
and saliva to detect drug use. Drug Alcohol Rev. 2004, 23(2), 213-7. 
[20] 
Maurer, H.H. Analytical Toxicology. EXS. 2010, 100, 317-37. 
[21] 
Shearer, D.S.; Baciewicz, G.J.; Kwong, T.C. Drugs of abuse testing in a 
psychiatric outpatient service. Clin. Lab. Med. 1998, 18(4),713-26. 
[22] 
DuPont, R. L. Drug testing in clinical settings. Journal of Global Drug Policy 
and Practice, 2010, 3(4). 
[23] 
Randall W.C.; American J. Phys. Med.1953, 32, 292. 
[24] 
Eichna L.W.; Bean W.B.; Ashe W.F.; Nelson N. Bull. Johns Hopkins Hosp. 
ACKNOWLEDGEMENT  
Case 1:21-cr-10270-MLW     Document 70-5     Filed 04/06/22     Page 15 of 17

560    Current Medicinal Chemistry,  2013, Vol. 20, No. 4 
De Giovanni and Fucci 
1945, 76, 25. 
[25] 
Levisky, J.A.; Bowerman, D.L.; Jenkins, W.W.; Karch, S.B. Drug deposition 
in adipose tissue and skin: evidence for an alternative source of positive 
sweat patch tests. Forensic Sci. Int. 2000, 110(1), 35-46. 
[26] 
Chawarski, M.C.; Fiellin, D.A.; O'Connor, P.G.; Bernard, M.; Schottenfeld, 
R.S. Utility of sweat patch testing for drug use monitoring in outpatient 
treatment for opiate dependence. J. Subst. Abuse Treat. 2007, 33(4),411-5. 
[27] 
Brunet, B.R.; Barnes, A.J.; Choo, R.E.; Mura, P.; Jones, H.E.; Huestis, M.A. 
Monitoring pregnant women's illicit opiate and cocaine use with sweat test-
ing. Ther. Drug Monit. 2010, 32(1), 40-9. 
[28] 
Huestis M.A.; Cone, E.J. Alternative testing matrices in Karch SB. Drug 
abuse Handbook Boca Raton CRC Press 1998. 
[29] 
Inaba T. Cocaine: pharmacokinetics and biotransformation in man. Can. J. 
Physiol. Pharmacol. 1989, 67(9), 1154-7. Review. 
[30] 
Kacinko, S.L.; Barnes, A.J; Schwilke, E.W.; Cone, E.J.; Moolchan, E.T.; 
Huestis, M.A. Disposition of cocaine and its metabolites in human sweat af-
ter controlled cocaine administration. Clin. Chem. 2005, 51(11), 2085-94. 
[31] 
Uemura, N.; Nath, R.P.; Harkey, M.R.; Henderson, G.L.; Mendelson, J.; 
Jones, R.T. Cocaine levels in sweat collection patches vary by location of 
patch placement and decline over time. J. Anal. Toxicol. 2004, 28(4), 253-9. 
[32] 
Schwilke, E.W.; Barnes, A.J.; Kacinko, S.L.; Cone, E.J.; Moolchan, E.T.; 
Huestis, M.A. Opioid disposition in human sweat after controlled oral co-
deine administration. Clin. Chem. 2006, 52(8),1539-45. 
[33] 
Walter K.; Kurz H. Binding of drugs to human skin: influencing factors and 
the role of tissue lipids. J. Pharm. Pharmacol. 1988, 40, 689-93. 
[34] 
Faergermann J.; Zehender H.; Denouel J.; Millerioux L. Levels of terbinafine 
in plasma, stratum corneum, dermis-epidermis (without stratum corneum) 
sebum, hair, and nails during and after 250 mg terbinafine orally once per 
day for four weeks. Acta Derm. Venereol. 1993, 73, 305-9. 
[35] 
Burns M.; Baselt R.C. Monitoring drug use with a sweat patch: an experi-
ment with cocaine.J. Anal.Toxicol. 1985, 19, 41-48. 
[36] 
Joseph, R.E. Jr.; Oyler, J.M.; Wstadik, A.T.; Ohuoha, C.; Cone, E.J. Drug 
testing with alternative matrices I. Pharmacological effects and disposition of 
cocaine and codeine in plasma, sebum, and stratum corneum. J. Anal. Toxi-
col. 1998, 22(1), 6-17. 
[37] 
Liberty, H.J.; Johnson, B.D.; Fortner, N. Detecting cocaine use through 
sweat testing: multilevel modeling of sweat patch length-of-wear data. J. 
Anal. Toxicol. 2004, 28(8), 667-73. 
[38] 
Kidwell, D.A.; Kidwell, J.D.; Shinohara, F.; Harper, C.; Roarty, K.; Bernadt, 
K.; McCaulley, R.A.; Smith, F.P. Comparison of daily urine, sweat, and skin 
swabs among cocaine users. Forensic Sci. Int. 2003, 133(1-2), 63-78. 
[39] 
Pichini, S.; Navarro, M.; Pacifici, R.; Zuccaro, P.; Ortuño, J.; Farré, M.; 
Roset, P.N.; Segura, J. ; de la Torre, R. Usefulness of sweat testing for the 
detection of MDMA after a single-dose administration. J. Anal. Toxicol. 
2003, 27(5), 294-303. 
[40] 
Balabanova, S.; Schneider, E.; Wepler, R.; Hermann, B.; Boschek, H.J.; 
Scheitler, H. Significance of drug determination in pilocarpine sweat for de-
tection of past drug abuse. Beitr. Gerichtl Med. 1992, 50,111-5. 
[41] 
Cole, D.E.; Boucher, M.J. Use of a new sample-collection device (Macro-
duct) in anion analysis of human sweat. Clin. Chem. 1986, 32(7), 1375-8. 
[42] 
Spiehler, V.; Fay, J.; Fogerson, R.; Schoendorfer, D.; Niedbala, R.S. Enzyme 
immunoassay validation for qualitative detection of cocaine in sweat. Clin. 
Chem. 1996, 42(1), 34-8. 
[43] 
Burns, M.; Baselt, R.C. Monitoring drug use with a sweat patch: an experi-
ment with cocaine. J. Anal. Toxicol. 1995, 19(1), 41-8. 
[44] 
Skopp, G.; Pötsch, L.; Eser, H.P.; Möller, M.R. Preliminary practical find-
ings on drug monitoring by a transcutaneous collection device. J. Forensic 
Sci. 1996, 41(6), 933-7. 
[45] 
Kintz, P.; Tracqui, A.; Mangin, P. Sweat testing for benzodiazepines. J. 
Forensic Sci. 1996, 41(5), 851-4. 
[46] 
Kintz, P.; Tracqui, A.; Jamey, C.; Mangin, P. Detection of codeine and 
phenobarbital in sweat collected with a sweat patch. J. Anal. Toxicol. 1996, 
20(3), 197-201. 
[47] 
Liberty, H.J.; Johnson, B.D.; Fortner, N.; Randolph, D. Detecting crack and 
other cocaine use with fastpatches. Addict Biol. 2003, 8(2), 191-200. 
[48] 
Fogerson, R.; Schoendorfer, D.; Fay, J.; Spiehler, V. Qualitative detection of 
opiates in sweat by EIA and GC-MS. J. Anal. Toxicol. 1997, 21(6), 451-8. 
[49] 
Balabanova, S.; Schneider, E. Detection of drugs in sweat. Beitr. Gerichtl 
Med. 1990, 48, 45-9. 
[50] 
Moody, D.E.; Cheever, M.L. Evaluation of immunoassays for semiquantita-
tive detection of cocaine and metabolites or heroin and metabolites in ex-
tracts of sweat patches. J. Anal. Toxicol. 2001, 25(3), 190-7. 
[51] 
Moody, D.E.; Spanbauer, A.C.; Taccogno, J.L.; Smith, E.K. Comparative 
analysis of sweat patches for cocaine (and metabolites) by radioimmunoas-
say and gas chromatography-positive ion chemical ionization-mass spec-
trometry. J. Anal. Toxicol. 2004, 28(2), 86-93. 
[52] 
Mura, P.; Kintz, P.; Papet, Y.; Ruesch, G.; Piriou, A. Evaluation of six rapid 
tests for screening of cannabis in sweat, saliva and tears. Acta Clin Belg 
Suppl. 1999, 1, 35-8. 
[53] 
Samyn, N.; Van Haeren, C. On-site testing of saliva and sweat with drugwipe 
and determination of concentrations of drugs of abuse in saliva, plasma and 
urine of suspected users. International Journal of Legal Medicine, 
2000,113(3), 150-154. 
[54] 
Pacifici, R.; Farré, M.; Pichini, S.; Ortuño, J.; Roset, P.N.; Zuccaro, P.; 
Segura, J.; de la Torre, R. Sweat testing of MDMA with the Drugwipe ana-
lytical device: a controlled study with two volunteers. J. Anal. Toxicol. 2001, 
25 (2),144-6. 
[55] 
Hazarika, P.; Jickells, S.M.; Wolff, K.; Russell, D.A. Multiplexed detection 
of metabolites of narcotic drugs from a single latent fingermark. Anal. Chem. 
2010, 82 (22), 9150-4. 
[56] 
Henderson, G.L.; Wilson, B.K. Excretion of methadone and metabolites in 
human sweat. Res. Commun. Chem. Pathol. Pharmacol. 1973, 5 (1), 1-8. 
[57] 
Fay,J.; Fogerson, R.; Schoendorfer, D.; Niedbala, R.S.; Spiehler, V. Detec-
tion of methamphetamine in sweat by EIA and GC-MS. J. Anal. Toxicol. 
1996, 20 (6), 398-403. 
[58] 
Maurer, H.H.; Arlt, J.W.; Kraemer, T.; Schmitt, C.J.; Weber, A.A. Analytical 
development for low molecular weight xenobiotic compounds. Arch. Toxi-
col. Suppl. 1997, 19, 189-97. 
[59] 
Segura, J.; Ventura, R.; Jurado, C. Derivatization procedures for gas chroma-
tographic-mass spectrometric determination of xenobiotics in biological 
samples, with special attention to drugs of abuse and doping agents. J. 
Chromatogr. B Biomed. Sci. Appl. 1998, 21,713(1),61-90. 
[60] 
Kintz, P.; Henrich, A.; Cirimele, V.; Ludes, B. Nicotine monitoring in sweat 
with a sweat patch. J. Chromatogr. B Biomed. Sci. Appl. 1998,705 (2), 357-
61. 
[61] 
Preston, K.L.; Huestis, M.A.; Wong, C.J.; Umbricht, A.; Goldberger, B.A.; 
Cone, E.J. Monitoring cocaine use in substance-abuse-treatment patients by 
sweat and urine testing. J. Anal. Toxicol. 1999, 23 (5),313-22. 
[62] 
Huestis, M.A.; Cone, E.J.; Wong, C.J.; Umbricht, A.; Preston, K.L. Monitor-
ing opiate use in substance abuse treatment patients with sweat and urine 
drug testing. J. Anal. Toxicol. 2000, 24 (7),509-21. 
[63] 
Kintz, P.; Villain, M.; Cirimele, V.; Goullé, J.P.; Ludes, B. Crime under the 
influence of psychoactive drugs: the problem of the duration of detection. 
Acta Clin. Belg. Suppl. 2002 (1), 24-30. 
[64] 
Samyn, N.; De Boeck, G.; Verstraete, A.G. The use of oral fluid and sweat 
wipes for the detection of drugs of abuse in drivers. J. Forensic Sci. 2002, 
47(6),1380-7. 
[65] 
Saito, T.; Wtsadik, A.; Scheidweiler, K.B.; Fortner, N.; Takeichi, S.; Huestis, 
M.A. Validated gas chromatographic-negative ion chemical ionization mass 
spectrometric method for delta(9)-tetrahydrocannabinol in sweat patches. 
Clin. Chem. 2004, 50 (11), 2083-90. 
[66] 
Follador, M.J.; Yonamine, M.; de Moraes Moreau, R.L.; Silva, O.A. Detec-
tion of cocaine and cocaethylene in sweat by solid-phase microextraction and 
gas chromatography/mass spectrometry. J. Chromatogr. B Analyt. Technol. 
Biomed. Life Sci. 2004, 811(1) 37-40. 
[67] 
Pichini, S.; Abanades, S.; Farré, M.; Pellegrini, M.; Marchei, E.; Pacifici, R.; 
de la Torre, L.; Zuccaro, P. Quantification of the plant-derived hallucinogen 
Salvinorin A in conventional and non-conventional biological fluids by gas 
chromatography/mass spectrometry after Salvia divinorum smoking. Rapid 
Commun. Mass Spectrom. 2005, 19 (12),1649-56. 
[68] 
Yang W.; Varnes A.J.; Ripple M.G.; Fowlere D.R.; Cone EJ; Moolchan E.T.; 
Chung H.; Huestis MA Simultaneuos quantification of metanfetamine, co-
caine, codeine, and metabolites in skin by positive chemical ionization gas 
chromatography –mass spectrometry. J. Chromatogr. 2006, 833, 210-8. 
[69] 
Abanades, S.; Farré, M.; Segura, M.; Pichini, S.; Pastor, A.; Pacifici, R.; 
Pellegrini, M.; de la Torre, R. Disposition of gamma-hydroxybutyric acid in 
conventional and nonconventional biologic fluids after single drug admini-
stration: issues in methodology and drug monitoring. Ther. Drug. Monit. 
2007, 29(1),64-70. 
[70] 
De Martinis, B.S.; Barnes, A.J.; Scheidweiler, K.B.; Huestis, M.A. Devel-
opment and validation of a disk solid phase extraction and gas chromatogra-
phy-mass spectrometry method for MDMA, MDA, HMMA, HMA, MDEA, 
methamphetamine and amphetamine in sweat. J. Chromatogr. B Analyt. 
Technol. Biomed. Life Sci. 2007, 852(1-2), 450-8. 
[71] 
Brunet, B.R.; Barnes, A.J.; Scheidweiler, K.B.; Mura, P.; Huestis, M.A. 
Development and validation of a solid-phase extraction gas chromatography-
mass spectrometry method for the simultaneous quantification of methadone, 
heroin, cocaine and metabolites in sweat. Anal. Bioanal. Chem. 2008, 392(1-
2), 115-27. 
[72] 
Fucci, N.; De Giovanni, N.; Scarlata, S. Sweat testing in addicts under 
methadone treatment: An italian experience. Forensic Sci. Int. 2008 174 (2-
3), 107-110. 
[73] 
Barnes, A.J.; De Martinis, B.S.; Gorelick, D.A.; Goodwin, R.S.; Kolbrich, 
E.A.; Huestis, M.A. Disposition of MDMA and metabolites in human sweat 
following controlled MDMA administration. Clin. Chem. 2009, 55(3),454-
62. 
[74] 
Barnes, A.J.; Brunet, B.R.; Choo, R.E.; Mura, P.; Johnson, R.E.; Jones, H.E.; 
Huestis, M.A. Excretion of methadone in sweat of pregnant women through-
out gestation after controlled methadone administration. Ther. Drug. Monit. 
2010, 32(4),497-503. 
[75] 
Concheiro, M.; Shakleya, D.M.; Huestis, M.A. Simultaneous analysis of 
buprenorphine, methadone, cocaine, opiates and nicotine metabolites in 
sweat by liquid chromatography tandem mass spectrometry. Anal. Bioanal. 
Chem. 2011, 400 (1), 69-78. 
[76] 
Marchei, E.; Farré, M.; Pardo, R.; Garcia-Algar, O.; Pellegrini, M.; Pacifici, 
R.; Pichini, S. Usefulness of sweat testing for the detection of methylpheni-
date after fast- and extended-release drug administration: a pilot study. Ther. 
Drug. Monit. 2010, 32(4),508-11. 
[77] 
Cirimele, V.; Kintz, P.; Gosselin, O.; Ludes, B. Clozapine dose-
concentration relationships in plasma, hair and sweat specimens of schizo-
Case 1:21-cr-10270-MLW     Document 70-5     Filed 04/06/22     Page 16 of 17

Sweat Testing for Drugs of Abuse 
Current Medicinal Chemistry,  2013, Vol. 20, No. 4      561 
phrenic patients. For. Sci. Int. 2000,107(1-3),289-300. 
[78] 
Al-Dirbashi, O.Y.; Ikeda, K.; Takahashi, M.; Kuroda, N.; Ikeda, S.; Naka-
shima, K. Drugs of abuse in a non-conventional sample; detection of meth-
amphetamine and its main metabolite, amphetamine in abusers' clothes by 
HPLC with UV and fluorescence detection. Biomed. Chromatogr. 2001, 
15(7), 457-63. 
[79] 
Crouch, D.J.; Cook, R.F.; Trudeau, J.V.; Dove, D.C.; Robinson, J.J.; Web-
ster, H.L.; Fatah, A.A. The detection of drugs of abuse in liquid perspiration. 
J. Anal. Toxicol. 2001, 25(7), 625-7. 
[80] 
Kintz, P.; Tracqui, A.; Marzullo, C.; Darreye, A.; Tremeau, F.; Greth, P.; 
Ludes, B. Enantioselective analysis of methadone in sweat as monitored by 
liquid chromatography/ion spray-mass spectrometry. Ther. Drug. Monit. 
1998, 20 (1), 35-40. 
[81] 
Samyn, N.; De Boeck, G.; Wood, M.; Lamers, C.T.; De Waard, D.; Brook-
huis, K.A.; Verstraete, A.G.; Riedel, W.J. Plasma, oral fluid and sweat wipe 
ecstasy concentrations in controlled and real life conditions. For. Sci.Int. 
2002, 128 (1-2), 90-7. 
[82] 
Gallardo, E.; Barroso, M.; Queiroz, J.A. LC-MS: a powerful tool in work-
place drug testing. Drug Test. Anal. 2009, 3, 109-15. 
[83] 
Marchei, E.; Papaseit, E.; Garcia-Algar, O.Q.; Farrè, M.; Pacifici, R.; Pichini, 
S. Determination of atomoxetine and its metabolites in conventional and 
non-conventional biological matrices by liquid chromatography-tandem mass 
spectrometry. J. Pharm. Biomed. Anal. 2012, 60, 26-31. 
[84] 
Kintz, P.; Tracqui, A.; Mangin, P.; Edel, Y. Sweat testing in opioid users 
with a sweat patch. J. Anal. Toxicol. 1996, 20 (6), 393-7. 
[85] 
Taylor, J.R.; Watson, I.D.; Tames, F.J.; Lowe, D. Detection of drug use in a 
methadone maintenance clinic: sweat patches versus urine testing. Addiction. 
1998, 93 (6), 847-53. 
[86] 
Levisky, J.A.; Bowerman, D.L.; Jenkins, W.W.; Johnson, D.G.; Levisky, 
J.S.; Karch, S.B. Comparison of urine to sweat patch test results in court or-
dered testing. For. Sci. Int. 2001, 122(1), 65-8. 
[87] 
de la Torre, R.; Farré, M.; Navarro, M.; Pacifici, R.; Zuccaro, P.; Pichini, S. 
Clinical pharmacokinetics of amfetamine and related substances: monitoring 
in conventional and non-conventional matrices. Clin. Pharmacokinet. 
2004,43(3),157-85. 
[88] 
Suzuki,S.; Inoue, T.; Hori, H.; Inayama, S. Analysis of methamphetamine in 
hair, nail, sweat, and saliva by mass fragmentography. J. Anal. Toxicol. 
1989, 13(3),176-8. 
[89] 
Barnes, A.J.; Smith, M.L.; Kacinko, S.L.; Schwilke, E.W.; Cone, E.J.; Mool-
chan, E.T.; Huestis, M.A. Excretion of methamphetamine and amphetamine 
in human sweat following controlled oral methamphetamine administration.. 
Clin Chem. 2008, 54(1),172-80. 
[90] 
Kintz, P. Excretion of MBDB and BDB in urine, saliva, and sweat following 
single oral administration. J. Anal. Toxicol. 1997, 21(7),570-5. 
[91] 
Kintz, P.; Samyn, N. Determination of "Ecstasy" components in alternative 
biological specimens. J. Chromatogr. B Biomed. Sci. Appl. 1999, 733 (1-
2),137-43. 
[92] 
De Martinis, B.S. Sweat as an alternative matrix for amphetamines and 
methylenedioxy derivatives analysis. Current Pharmaceutical Analysis 2008, 
4(4), 274-278. 
[93] 
de la Torre, R.; Pichini, S. Usefulness of sweat testing for the detection of 
cannabis smoke. Clin. Chem. 2004, 50(11), 1961-2. 
[94] 
Johansson, E.; Norén, K.; Sjövall, J.; Halldin, M.M. Determination of delta 
1-tetrahydrocannabinol in human fat biopsies from marihuana users by gas 
chromatography-mass spectrometry. Biomed. Chromatogr. 1989, 3(1),  
35-38. 
[95] 
Staub, C. Chromatographic procedures for determination of cannabinoids in 
biological samples with special attention to blood and alternative matrices 
like hair, saliva, sweat and meconium. J. Chromatogr. B 733, 1999, 119-126. 
[96] 
Kintz, P.; Cirimele, V.; Ludes, B. Detection of cannabis in oral fluid (saliva) 
and forehead wipes (sweat) from impaired drivers. J. Anal. Toxicol. 2000, 
24(7), 557-61. 
[97] 
Huestis, M.A.; Scheidweiler, K.B.; Saito, T.; Fortner, N.; Abraham, T.; 
Gustafson, R.A.; Smith, M.L. Excretion of Delta9-tetrahydrocannabinol in 
sweat. For. Sci. Int. 2008, 174 (2-3),173-7. 
[98] 
Winhusen, T.M.; Somoza, E.C.; Singal, B.; Kim, S.; Horn, P.S.; Rotrosen, J. 
Measuring outcome in cocaine clinical trials: a comparison of sweat patches 
with urine toxicology and participant self-report. Addiction 2003 98 (3), 317-
24. 
[99] 
Kintz, P.; Cirimele, V.; Ludes, B. Codeine testing in sweat and saliva with 
the Drugwipe. Int. J. Legal Med. 1998, 111(2), 82-4. 
[100] 
Balabanova, S.; Schneider, E.; Bühler, G.; Krause, H. Presence of methadone 
in apocrine sweat of the human. Z. Rechtsmed. 1990, 103 (5)323-7. 
[101] 
Concheiro, M.; Jones, H.E.; Johnson, R.E.; Choo, R.; Huestis, M.A. Prelimi-
nary buprenorphine sublingual tablet pharmacokinetic data in plasma, oral 
fluid, and sweat during treatment of opioid-dependent pregnant women. 
Ther. Drug Monit. 2011, 33(5), 619-26. 
[102] 
Balabanova, S.; Krupienski, M. Detection of nicotine in eccrine sweat after 
stimulation of sweat glands during nicotine withdrawal. Hautarzt. 1995, 
46(4), 255-8. 
[103] 
Ishiyama,I.; Nagai, T.; Nagai, T.; Komuro, E.; Momose, T.; Akimori, N.The 
significance of drug analysis of sweat in respect to rapid screening for drug 
abuse. Z. Rechtsmed. 1979, 8, 82(4), 251-6. 
[104] 
Marchei, E.; Farrè, M.; Pellegrini, M.; Garcia-Algar O.; Vall O.; Pacifici, R., 
Pichini, S. Pharmacokinetics of methylphenidate in oral fluid and sweat of a 
pediatric subject. Forensic Sci. Int. 2010, 196(1-3), 59-63. 
[105] 
Lankheet, N.A.G. ;Blank, C.U.; Mallo, H.; Adriaansz, S. ;Rosing, H.; Schel-
lens, J.H.M.; Huitema, A.D.R.; Beijnen, J.H. Determination of sunitinib and 
its active methabolite N-desethylsunitinib in sweat of a patient. 
J.Anal.Toxicol. 35, 2011, 558-565. 
[106] 
Verstraete, A.; Puddu, M. Evaluation of different roadsite drug tests – Brux-
elles: European Commition 2000 (Project Profile: ROSITA). 
[107] 
Samyn, N.; Verstraete, A. On-site testing for drugs of abuse in urine, saliva 
and sweat. Vor-ort-tests zur drogenerkennung in urin, speichel und schweiss. 
Blutalkohol 2000, 37(2), 58-69. 
[108] 
Kintz, P.; Cirimele, V.; Mairot, F.; Muhlmann, M.; Ludes, B. Drug tests on 
198 drivers involved in an accident. Presse Med. 2000, 29(23) 1275-8. 
[109] 
Walsh, J.M.; de Gier, J.J.; Christopherson, A.S.; Verstraete, A.G. Drugs and 
driving. Traffic Inj. Prev. 2004 (3) 241-53. 
[110] 
Rivier, L. Techniques for analytical testing of unconventional samples. 
Baillieres Best Pract. Res. Clin. Endocrinol. Metab. 2000, 14(1),147-65. 
[111] 
Rivier, L. Analytical testing for sporting doping on alternative biological 
samples. Biology of sport, 2000, ,17, 87-106. 
[112] 
Huestis, M.A.; Choo, R.E. Drug abuse's smallest victims: in utero drug 
exposure. Forensic Sci. Int. 2002, 128(1-2), 20-30. 
[113] 
Lozano, J.; García-Algar, O.; Vall, O.; de la Torre, R.; Scaravelli, G. Pichini, 
S. Biological matrices for the evaluation of in utero exposure to drugs of 
abuse. Ther Drug Monit. 2007, 29(6),711-34. 
[114] 
Gray, T.; Huestis, M. Bioanalytical procedures for monitoring in utero drug 
exposure. Anal. Bioanal. Chem. 2007 388(7),1455-65. 
[115] 
Daughton, C.G. Illicit drugs: contaminants in the environment and utility in 
forensic epidemiology. Rev. Environ. Contam. Toxicol. 2011, 210, 59-110. 
 
 
 
Received: June 28, 2012 
Revised: November 29, 2012 
Accepted: December 12, 2012 
 
 
Case 1:21-cr-10270-MLW     Document 70-5     Filed 04/06/22     Page 17 of 17

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