The use of saliva as an unconventional sample for drug detection: A review
Author(s): Shikha Shrivastava, Bastian TS, Anil Singh, Rohit Jaiswal
Vol. 8, No. 2 (2008-07 - 2008-12)
Shikha Shrivastava٭, Bastian TS٭٭, Anil Singh٭٭٭, Rohit Jaiswal٭٭٭٭
Department of Oral Pathology and Microbiology, Sardar Patel Post Graduate Institute of Dental and Medical Sciences, Lucknow 226025
Abstract
Global trends in drug trafficking and drug usage patterns
indicate a continuing pattern of escalation throughout the
world. Over the last two decades, urine analysis has evolved
into a highly accurate means for determining whether
individuals have been exposed to illicit drugs of abuse.
Advances have also been made in the use of alternate
biological matrices such as hair, oral fluids and sweat for drug
testing. This review evaluates the use of saliva in drug analysis
and in therapeutic and toxicological monitoring.
Keywords: saliva, drug detection, collection of saliva
Introduction
Testing for drugs of abuse evolved in United States during
the 1960s within the armed forces. The purpose of drug testing
is to determine whether an individual has used any particular
substance that might have affected their well-being or
behaviour. The most common scenarios where testing is
undertaken to detect psychoactive drug use include workplace
drug testing, forensic drug testing (e.g. with drugs and driving)
and compliance with treatment1.
Drug testing has undergone major advances, particularly
over the last 10 years. The use of alternative specimens to
blood or urine for establishing exposure to drugs has become
a significant direction in clinical and forensic toxicology. These
alternative specimens include hair, sweat and oral fluid. Oral
fluid has been seen as a non-invasive alternative to blood but
also as an alternative to urine when substitution or
adulteration is suspected.
This review outlines the roles and applications of testing
for drugs in oral fluid, describes the relative advantages and
disadvantages of this form of testing and illustrates
applications of oral fluid testing for specific drugs.
Oral Fluid as a Drug-Testing Specimen
Oral fluid, sometimes called “mixed saliva,” comes from
three major and several minor salivary glands. Strictly speaking,
oral fluid is the mixed saliva from the glands and other
constituents present in the mouth.
Oral fluid contains plasma electrolytes such as potassium,
sodium, chloride, and bicarbonate and many other plasma
constituents, such as enzymes, immunoglobulins, and DNA.
The total volume of oral fluid produced by an adult may be in
excess of 1000 ml/day with typical flows of 0.05 ml/min while
sleeping, 0.5 ml/min while spitting, and 1 ml/min to 3 ml/min
while chewing gum2.
A number of drugs are known to affect the secretion of
oral fluid. Most commonly these are amphetamines, including
the designer forms such as ecstasy (MDMA), and cannabis.
Other drugs include the sedating antihistamines, antipsychotic
drugs, anticholinergic drugs and a number of antidepressants.
There are less commonly used drugs that increase flow and
these include clonidine, pilocarpine and beta-2 stimulants
(salbutamol, terbutaline etc)2.
Many drugs of interest in the criminal justice setting have
been detected in oral fluid, including ethanol,
methamphetamine, amphetamine, barbiturates,
benzodiazepines, heroin, cocaine, cannabinoids, marijuana,
nicotine, opioids and phencyclidine3.
Mechanisms of drug transfer from blood to saliva
Landon and Mahmod (1982) suggested that the possible
routes which may lead to a drug being present in mixed saliva
are passive transcellular diffusion, ultrafiltration, active
transport and pinocytosis. However, there is no evidence that
pinocytosis plays any role4.
Mechanisms of salivary drug transport
Most drugs appear to enter saliva by a simple passive
diffusion process which is characterized by the transfer of drug
molecules down a concentration gradient. Paxton (1979)
suggested that the rate of diffusion of a drug is a function of
the concentration gradient, the surface area over which the
transfer occurs, the thickness of the membrane, and a diffusion
constant that depends on the physico-chemical properties of
each drug (molecular weight, dissociation constants, lipid solubility, and protein binding)4. Although less common, low molecular mass compounds can also be transferred into oral
fluid by active secretion or diffusion through pores in the
membrane3.
Concentration of lipid-insoluble, non-electrolytes in saliva
as a function of molecular size4.
Collection of saliva
A variety of methods are available for collecting saliva.
Some involve stimulating saliva production, while others target
collection of unstimulated or nonstimulated saliva.
According to Navazesh (1993) unstimulated saliva can be
collected by the draining method, which is performed by
allowing saliva to drip from the mouth into a collection
container. Several techniques may be used to collect stimulated
saliva. The simplest involves tongue, cheek, or lip movements
without the use of an external stimulus. Chewing paraffin wax,
parafilm, teflon, rubber bands, gum base, or chewing gum are
usually referred to as mechanical methods of stimulating saliva
production. A lemon drop or citric acid can be placed in the
mouth to provide a gustatory stimulus for saliva production5.
Following stimulation by one or more of these methods,
saliva can be spit, suctioned, or swabbed from the mouth.
Some collection techniques combine stimulation and collection
of the saliva using absorbent materials such as cotton balls or
cotton rolls. After the absorbent material becomes saturated
with saliva, it is removed from the mouth and the saliva is
extracted by centrifugation or by applying pressure to the
material4.
There are several potential problems associated with
stimulating saliva production. Chang (1976) showed that
parafilm absorb some drugs and therefore, give erroneous
results when saliva is tested for drugs or drug metabolites.
Also, paraffin contains compounds that may affect
chromatographic analyses—again affecting drug testing
accuracy. Some salivary stimulants may change the salivary
composition and, therefore, affect the saliva-drug
concentration. For example, citric acid may change saliva pH
and consequently alter drug concentrations in the saliva. Citric
acid and cotton have also been shown to alter immunoassay
drug test results4.
Several devices are commercially available for collecting
saliva. Some devices are based on the collection techniques just
discussed. They carry names such as Oral Diffusion Sink®
(Shipley et al., 1992; Hold et al., 1996), Proflow SialometerTM
(Jones, 1995), Orasure® (Gomez et al., 1994), and
SalivetteTM` (Shipley et al., 1992). They have been advocated
for saliva collection when testing for ethanol, steroids, and
many other drugs6.
Analytical methodology for the measurement of drugs in saliva
Pre-analytical manipulations
Once the samples have been collected, it is important that
they be properly stored unless analyses are to be performed
immediately. Opinions differ as to the procedure to be
followed, but most workers freeze the sample to -20°C, while
some workers recommend centrifugation before freezing and
others recommend centrifugation after thawing and prior to
analysis. In forensic work in which saliva samples have been
taken primarily for serological purposes, it is common practice
to subject the sample and container to boiling water
temperatures for 15-30 minutes prior to freezing. Only in cases
in which the toxic material present in saliva is volatile or heatunstable
would this treatment be expected to be deleterious to
later analysis of such saliva samples7.
Most authors use the centrifugate, either by extracting the
centrifugate with an organic solvent at a desirable pH or by
using the centrifugate directly in the analytical process without
sample pretreatment (Roth, Beschke, Jauch, Zimmer and Koss,
1981). Caddy (1984) has extensively reviewed the different
methods of analysis of saliva4.
Immunological methods
Immunological methods of analysis have been widely used
for monitoring drugs in saliva and other body fluids, mainly
because of their relative simplicity of use, requiring little or no
extractive operations, their application to large batch analyses,
and their sensitivity. Paxton and Donald (1980) in their studies
found that they do, however, suffer from disadvantages in that
they do not always possess the specificity required for
distinguishing metabolites from the parent drug.
Radioimmunoassay (RIA) techniques have been used especially
for the analysis of hormones in saliva, such as estradiol,
progesterone, testosterone, cortisol, and cortisone. Other
drugs, which have been measured with RIA are for instance,
cocaine, cannabinoids, haloperidol, theophylline and cotinine4.
The use of the alternative non-radioactive immunological
procedure, an enzyme multiplied immunoassay technique
(EMIT®), is based on competitive protein binding using an
enzyme as a label and an antibody as a specific binding
protein. The enzyme activity is related to the amount of drug
in the sample and is measured spectrophotometrically.
Although this assay is very easy to use and requires no
radiochemical facilities, it is not used very often for monitoring
saliva levels. Sensitivity may be one major reason for this. One
has to be careful to use citric acid in combination with the
EMIT® assay because the enzyme glucose-6- phosphate
dehydrogenase (G6PD) used in the EMIT® assay for
ethosuximide and phenytoin is inhibited 38% by citric acid4.
Another direct immunoassay which is not subject to the
disadvantages associated with the use of radioisotopes in RIA
is described by De Boever et al. (1990). They developed a
chemiluminescence immunoassay (CIA) using isoluminol for
the detection of estradiol in saliva. Cai, Zhu and Chen (1993)
measured phenytoin in 1 ml saliva samples by fluorescence
polarization (FPIA)4.
Chromatographic methods
Thin-layer chromatography (TLC) has the advantage of
simplicity and allows the simultaneous determination of
several samples. However, the major limiting factor is the
detection of the respective spots on the thin-layer plate at low
drug levels in saliva. Therefore, this technique is not often used
in the drug monitoring of saliva. With the development of
High-Performance TLC (HPTLC), Drehsen and Rohdewald (1981)
tried to reach a higher sensitivity and precision. However, this
procedure did not found wider application for saliva drug
monitoring4.
The most popular analytical procedure for the
measurement at the nanogram or picogram level is based on
Gas Chromatography (GC), or, in the hyphenated mode, with
Mass Spectrometry (GC/MS). Thompson et al. (1987) detected
cocaine in saliva with GC/MS for 12 to 36 hours after
administration. Gould et al. (1986) developed a GC/MS procedure for the measurement of salivary testosterone in
female subjects, a striking application, because of the
inefficiency of RIA4.
Doping drugs in saliva
The most frequently used biological specimen for the
determination of drugs in doping control is urine, since only a
non-invasively obtained sample is acceptable for routine
collection. Yet, even the acceptability of urine sample is being
disputed in view of the potential invasion of privacy, especially
if a directly observed collection is advisable to prevent
adulteration or substitution of sample. That happens, for
instance, when athletes try to escape detection by using urine
from someone else. Another major disadvantage of urine is the
variability in the renal clearance of drugs and their metabolites,
which is largely due to fluctuations in the flow rate and pH of
urine. Not all drugs are excreted in the urine, for instance, the
lipid soluble -blocking drugs tend to be rapidly eliminated by
various metabolism systems in the liver. At present, saliva is not
used as a biological fluid for doping control. Although a
qualitative doping control mainly depends on the sensitivity of
the assay, the usefulness of saliva needs to be explored here
further7.
Advantages and disadvantages of oral-fluid drug testing
As an alternative matrix for drug testing, oral fluid offers
some distinct advantages. The matrix is relatively clean and
readily accessible for sampling. Collection is easy, non-invasive,
and inexpensive. Sampling can be better supervised without
invasion of privacy, reducing the opportunity for sample
adulteration or substitution. Oral fluid testing also offers the
possibility of direct comparison of unbound, pharmacologically
active drug concentrations to pharmacodynamic effects3.
However, the oral fluid drug testing is associated with
certain disadvantages. These include variability of salivary flow
and pH, and a shorter detection window than urine for active
drugs. In addition, specimen collection can have a serious
impact on analytical findings and smaller volumes of oral fluid
are generally collected. Furthermore, there are few reports of
drug concentration data to guide interpretation of oral fluid
test results. Oral fluid drug concentrations often are lower than
concentrations in traditional biofluids requiring new and
sensitive analytical methodology. Certain drugs like, cannabis
derivatives and benzodiazepines do not pass readily from
blood into saliva while the concentration of some drugs is
exceptionally high, eg. morphine and codeine, because of
buccal absorption following smoking or snorting3.
Conclusions
Monitoring illicit drug use in drug treatment programs is
traditionally performed by analysis of urine. In recent years,
interest in other biological matrices as alternative drug-testing
tools has grown, with oral fluid as one of the most promising
new matrices. The use of oral fluid has been found to offer
significant promise when detection of relatively recent use of
drugs is sought in a non-invasive manner. Technological
advances do allow on site detection of drugs, but there are
technical issues in relation to collection of oral fluid and in the
variability of drug concentrations (of different drug types) in
this fluid. More research is needed to further the detection of
drugs present in this fluid, which should allow improved
reliability of detection of drugs. Similarly, future technological
developments of onsite devices should allow more sensitive
and reliable detection of a number of drugs.
References
- Cone EJ. Legal, workplace, and treatment drug testing with
alternate biological matrices on a global scale. Forensic
Science International 2001; 121 (1); 7-15.
- Aps JK, Martens LC. Review: The physiology of saliva and
transfer of drugs into saliva. Forensic Sci Int 2005; 150:
119-131.
- Dams R, Choo RE, Lambert WE, Jones H, Huestis MA. Oral
Fluid as an Alternative Matrix to Monitor Opiate and
Cocaine use in Substance Abuse Treatment Patients. Drug
Alcohol Depend 2007; 87(2-3): 258–267.
- Hold KM, de Boer D, Zuidema J, Maes RAA. Saliva as an
Analytical Tool in Toxicology. Int. J of Drug Testing 1995;
1(1): 1-36.
- Navazash H. Methods for collecting saliva. Ann NY Acad
Sci. 1993; 694: 72-77.
- Drummer OH. Drug Testing in Oral Fluid. Clin Biochem Rev
2006; 27: 117-129.
- Rai B: Oral Fluid in Toxicology. The Internet Journal of
Toxicology; 2007: 3(2).
Shikha Shrivastava٭, Bastian TS٭٭, Anil Singh٭٭٭, Rohit Jaiswal٭٭٭٭
Department of Oral Pathology and Microbiology, Sardar Patel Post Graduate Institute of Dental and Medical Sciences, Lucknow 226025
Abstract
Global trends in drug trafficking and drug usage patterns indicate a continuing pattern of escalation throughout the world. Over the last two decades, urine analysis has evolved into a highly accurate means for determining whether individuals have been exposed to illicit drugs of abuse. Advances have also been made in the use of alternate biological matrices such as hair, oral fluids and sweat for drug testing. This review evaluates the use of saliva in drug analysis and in therapeutic and toxicological monitoring.
Keywords: saliva, drug detection, collection of saliva
Introduction
Testing for drugs of abuse evolved in United States during the 1960s within the armed forces. The purpose of drug testing is to determine whether an individual has used any particular substance that might have affected their well-being or behaviour. The most common scenarios where testing is undertaken to detect psychoactive drug use include workplace drug testing, forensic drug testing (e.g. with drugs and driving) and compliance with treatment1.
Drug testing has undergone major advances, particularly over the last 10 years. The use of alternative specimens to blood or urine for establishing exposure to drugs has become a significant direction in clinical and forensic toxicology. These alternative specimens include hair, sweat and oral fluid. Oral fluid has been seen as a non-invasive alternative to blood but also as an alternative to urine when substitution or adulteration is suspected.
This review outlines the roles and applications of testing for drugs in oral fluid, describes the relative advantages and disadvantages of this form of testing and illustrates applications of oral fluid testing for specific drugs.
Oral Fluid as a Drug-Testing Specimen
Oral fluid, sometimes called “mixed saliva,” comes from three major and several minor salivary glands. Strictly speaking, oral fluid is the mixed saliva from the glands and other constituents present in the mouth.
Oral fluid contains plasma electrolytes such as potassium, sodium, chloride, and bicarbonate and many other plasma constituents, such as enzymes, immunoglobulins, and DNA. The total volume of oral fluid produced by an adult may be in excess of 1000 ml/day with typical flows of 0.05 ml/min while sleeping, 0.5 ml/min while spitting, and 1 ml/min to 3 ml/min while chewing gum2.
A number of drugs are known to affect the secretion of oral fluid. Most commonly these are amphetamines, including the designer forms such as ecstasy (MDMA), and cannabis. Other drugs include the sedating antihistamines, antipsychotic drugs, anticholinergic drugs and a number of antidepressants. There are less commonly used drugs that increase flow and these include clonidine, pilocarpine and beta-2 stimulants (salbutamol, terbutaline etc)2.
Many drugs of interest in the criminal justice setting have been detected in oral fluid, including ethanol, methamphetamine, amphetamine, barbiturates, benzodiazepines, heroin, cocaine, cannabinoids, marijuana, nicotine, opioids and phencyclidine3.
Mechanisms of drug transfer from blood to saliva
Landon and Mahmod (1982) suggested that the possible routes which may lead to a drug being present in mixed saliva are passive transcellular diffusion, ultrafiltration, active transport and pinocytosis. However, there is no evidence that pinocytosis plays any role4.
Mechanisms of salivary drug transport
Most drugs appear to enter saliva by a simple passive diffusion process which is characterized by the transfer of drug molecules down a concentration gradient. Paxton (1979) suggested that the rate of diffusion of a drug is a function of the concentration gradient, the surface area over which the transfer occurs, the thickness of the membrane, and a diffusion constant that depends on the physico-chemical properties of each drug (molecular weight, dissociation constants, lipid solubility, and protein binding)4. Although less common, low molecular mass compounds can also be transferred into oral fluid by active secretion or diffusion through pores in the membrane3.
Concentration of lipid-insoluble, non-electrolytes in saliva as a function of molecular size4.
Collection of saliva
A variety of methods are available for collecting saliva. Some involve stimulating saliva production, while others target collection of unstimulated or nonstimulated saliva. According to Navazesh (1993) unstimulated saliva can be collected by the draining method, which is performed by allowing saliva to drip from the mouth into a collection container. Several techniques may be used to collect stimulated saliva. The simplest involves tongue, cheek, or lip movements without the use of an external stimulus. Chewing paraffin wax, parafilm, teflon, rubber bands, gum base, or chewing gum are usually referred to as mechanical methods of stimulating saliva production. A lemon drop or citric acid can be placed in the mouth to provide a gustatory stimulus for saliva production5.
Following stimulation by one or more of these methods, saliva can be spit, suctioned, or swabbed from the mouth. Some collection techniques combine stimulation and collection of the saliva using absorbent materials such as cotton balls or cotton rolls. After the absorbent material becomes saturated with saliva, it is removed from the mouth and the saliva is extracted by centrifugation or by applying pressure to the material4.
There are several potential problems associated with stimulating saliva production. Chang (1976) showed that parafilm absorb some drugs and therefore, give erroneous results when saliva is tested for drugs or drug metabolites. Also, paraffin contains compounds that may affect chromatographic analyses—again affecting drug testing accuracy. Some salivary stimulants may change the salivary composition and, therefore, affect the saliva-drug concentration. For example, citric acid may change saliva pH and consequently alter drug concentrations in the saliva. Citric acid and cotton have also been shown to alter immunoassay drug test results4.
Several devices are commercially available for collecting saliva. Some devices are based on the collection techniques just discussed. They carry names such as Oral Diffusion Sink® (Shipley et al., 1992; Hold et al., 1996), Proflow SialometerTM (Jones, 1995), Orasure® (Gomez et al., 1994), and SalivetteTM` (Shipley et al., 1992). They have been advocated for saliva collection when testing for ethanol, steroids, and many other drugs6.
Analytical methodology for the measurement of drugs in saliva
Pre-analytical manipulations
Once the samples have been collected, it is important that they be properly stored unless analyses are to be performed immediately. Opinions differ as to the procedure to be followed, but most workers freeze the sample to -20°C, while some workers recommend centrifugation before freezing and others recommend centrifugation after thawing and prior to analysis. In forensic work in which saliva samples have been taken primarily for serological purposes, it is common practice to subject the sample and container to boiling water temperatures for 15-30 minutes prior to freezing. Only in cases in which the toxic material present in saliva is volatile or heatunstable would this treatment be expected to be deleterious to later analysis of such saliva samples7.
Most authors use the centrifugate, either by extracting the centrifugate with an organic solvent at a desirable pH or by using the centrifugate directly in the analytical process without sample pretreatment (Roth, Beschke, Jauch, Zimmer and Koss, 1981). Caddy (1984) has extensively reviewed the different methods of analysis of saliva4.
Immunological methods
Immunological methods of analysis have been widely used for monitoring drugs in saliva and other body fluids, mainly because of their relative simplicity of use, requiring little or no extractive operations, their application to large batch analyses, and their sensitivity. Paxton and Donald (1980) in their studies found that they do, however, suffer from disadvantages in that they do not always possess the specificity required for distinguishing metabolites from the parent drug.
Radioimmunoassay (RIA) techniques have been used especially for the analysis of hormones in saliva, such as estradiol, progesterone, testosterone, cortisol, and cortisone. Other drugs, which have been measured with RIA are for instance, cocaine, cannabinoids, haloperidol, theophylline and cotinine4. The use of the alternative non-radioactive immunological procedure, an enzyme multiplied immunoassay technique (EMIT®), is based on competitive protein binding using an enzyme as a label and an antibody as a specific binding protein. The enzyme activity is related to the amount of drug in the sample and is measured spectrophotometrically. Although this assay is very easy to use and requires no radiochemical facilities, it is not used very often for monitoring saliva levels. Sensitivity may be one major reason for this. One has to be careful to use citric acid in combination with the EMIT® assay because the enzyme glucose-6- phosphate dehydrogenase (G6PD) used in the EMIT® assay for ethosuximide and phenytoin is inhibited 38% by citric acid4. Another direct immunoassay which is not subject to the disadvantages associated with the use of radioisotopes in RIA is described by De Boever et al. (1990). They developed a chemiluminescence immunoassay (CIA) using isoluminol for the detection of estradiol in saliva. Cai, Zhu and Chen (1993) measured phenytoin in 1 ml saliva samples by fluorescence polarization (FPIA)4.
Chromatographic methods
Thin-layer chromatography (TLC) has the advantage of simplicity and allows the simultaneous determination of several samples. However, the major limiting factor is the detection of the respective spots on the thin-layer plate at low drug levels in saliva. Therefore, this technique is not often used in the drug monitoring of saliva. With the development of High-Performance TLC (HPTLC), Drehsen and Rohdewald (1981) tried to reach a higher sensitivity and precision. However, this procedure did not found wider application for saliva drug monitoring4.
The most popular analytical procedure for the measurement at the nanogram or picogram level is based on Gas Chromatography (GC), or, in the hyphenated mode, with Mass Spectrometry (GC/MS). Thompson et al. (1987) detected cocaine in saliva with GC/MS for 12 to 36 hours after administration. Gould et al. (1986) developed a GC/MS procedure for the measurement of salivary testosterone in female subjects, a striking application, because of the inefficiency of RIA4.
Doping drugs in saliva
The most frequently used biological specimen for the determination of drugs in doping control is urine, since only a non-invasively obtained sample is acceptable for routine collection. Yet, even the acceptability of urine sample is being disputed in view of the potential invasion of privacy, especially if a directly observed collection is advisable to prevent adulteration or substitution of sample. That happens, for instance, when athletes try to escape detection by using urine from someone else. Another major disadvantage of urine is the variability in the renal clearance of drugs and their metabolites, which is largely due to fluctuations in the flow rate and pH of urine. Not all drugs are excreted in the urine, for instance, the lipid soluble -blocking drugs tend to be rapidly eliminated by various metabolism systems in the liver. At present, saliva is not used as a biological fluid for doping control. Although a qualitative doping control mainly depends on the sensitivity of the assay, the usefulness of saliva needs to be explored here further7.
Advantages and disadvantages of oral-fluid drug testing
As an alternative matrix for drug testing, oral fluid offers some distinct advantages. The matrix is relatively clean and readily accessible for sampling. Collection is easy, non-invasive, and inexpensive. Sampling can be better supervised without invasion of privacy, reducing the opportunity for sample adulteration or substitution. Oral fluid testing also offers the possibility of direct comparison of unbound, pharmacologically active drug concentrations to pharmacodynamic effects3. However, the oral fluid drug testing is associated with certain disadvantages. These include variability of salivary flow and pH, and a shorter detection window than urine for active drugs. In addition, specimen collection can have a serious impact on analytical findings and smaller volumes of oral fluid are generally collected. Furthermore, there are few reports of drug concentration data to guide interpretation of oral fluid test results. Oral fluid drug concentrations often are lower than concentrations in traditional biofluids requiring new and sensitive analytical methodology. Certain drugs like, cannabis derivatives and benzodiazepines do not pass readily from blood into saliva while the concentration of some drugs is exceptionally high, eg. morphine and codeine, because of buccal absorption following smoking or snorting3.
Conclusions
Monitoring illicit drug use in drug treatment programs is traditionally performed by analysis of urine. In recent years, interest in other biological matrices as alternative drug-testing tools has grown, with oral fluid as one of the most promising new matrices. The use of oral fluid has been found to offer significant promise when detection of relatively recent use of drugs is sought in a non-invasive manner. Technological advances do allow on site detection of drugs, but there are technical issues in relation to collection of oral fluid and in the variability of drug concentrations (of different drug types) in this fluid. More research is needed to further the detection of drugs present in this fluid, which should allow improved reliability of detection of drugs. Similarly, future technological developments of onsite devices should allow more sensitive and reliable detection of a number of drugs.
References
- Cone EJ. Legal, workplace, and treatment drug testing with alternate biological matrices on a global scale. Forensic Science International 2001; 121 (1); 7-15.
- Aps JK, Martens LC. Review: The physiology of saliva and transfer of drugs into saliva. Forensic Sci Int 2005; 150: 119-131.
- Dams R, Choo RE, Lambert WE, Jones H, Huestis MA. Oral Fluid as an Alternative Matrix to Monitor Opiate and Cocaine use in Substance Abuse Treatment Patients. Drug Alcohol Depend 2007; 87(2-3): 258–267.
- Hold KM, de Boer D, Zuidema J, Maes RAA. Saliva as an Analytical Tool in Toxicology. Int. J of Drug Testing 1995; 1(1): 1-36.
- Navazash H. Methods for collecting saliva. Ann NY Acad Sci. 1993; 694: 72-77.
- Drummer OH. Drug Testing in Oral Fluid. Clin Biochem Rev 2006; 27: 117-129.
- Rai B: Oral Fluid in Toxicology. The Internet Journal of Toxicology; 2007: 3(2).
