Academy of Health Sciences, MCCS-HMP PA Branch, Fort Sam Houston, Texas 78234-6138, USA.
Amphetamine remains a widely abused drug throughout the world. It is also used therapeutically for weight loss, narcolepsy, and attention deficit disorder with hyperactivity (ADHD). ADHD has grown dramatically recently both in terms of diagnosis and treatment. Increasingly, older individuals are diagnosed and treated for ADHD, and treatment often continues into adulthood. Of the available treatments for ADHD, Adderall is widely prescribed. Despite its widespread use, there are no published data regarding the expected amphetamine excretion profile following its use. This is problematic because, in this case, medical review officers (MRO) and forensic toxicologists are asked to assess results in terms of use pursuant to valid medical prescription without specific data on which to base a sound decision. To address this situation, a study to determine the concentration and enantiomer composition of amphetamine excretion following administration of Adderall was undertaken. Adderall (20 mg) was administered to five healthy subjects with all subsequent ad lib urine samples (total urine void) collected for seven days. Adderall is a 3:1 mixture of d- and l-enantiomers of amphetamine salts. Peak amphetamine concentrations ranged from 2645 to 5948 ng/mL. Samples containing > or = 500 ng/mL of amphetamine (the administrative cutoff for a positive result by gas chromatography-mass spectrometry) were seen up to 47:30 h post dose. The number of samples that contained amphetamine concentrations of > or = 500 ng/mL ranged among individuals from 7 to 13. As anticipated, analysis showed the d-enantiomer to be in excess of the l-enantiomer, with the proportion of l-enantiomer increasing over time. Because of the mixture of enantiomers, not all samples that contained > or = 500 ng/mL of amphetamine were positive when tested by immunoassay. The drug concentration profiles were quite variable within and between subjects because of dilution and fluctuations in pH of the samples. These results are the first to describe the excretion of amphetamine following administration of Adderall. The presence of the l-enantiomer separates this drug from other preparations of the drug that are composed of only the d-enantiomer (i.e., dexedrine and much illicit amphetamine), thus readily differentiating them from Adderall use. Some illicit and medicinal amphetamine is, however, a mixture of amphetamine enantiomers. Because the enantiomers are metabolized at different rates, their proportion offers the opportunity to describe excretion versus time. Coupling this data with drug concentration makes it possible for forensic toxicologists and MROs to come to an informed decision about the involvement of this drug in a positive drug test result. Using the combination of enantiomer composition and quantitative data will allow MROs and forensic toxicologists to better assess the use of this drug from abuse of amphetamine.
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Academy of Health Sciences, MCCS-HMP PA Branch, Fort Sam Houston, Texas 78234-6138, USA.
Interpretation of drug testing results requires detailed scientific information, particularly in those cases where the question of legitimate use versus illicit use arises. Amphetamine remains a widely abused drug throughout the world, although it is also used therapeutically for weight loss, narcolepsy, and attention-deficit disorder with hyperactivity (ADHD). Treatment of ADHD using stimulant drugs is much more common now than it was in even the recent past. Increasingly, older individuals are diagnosed and treated for ADHD, and treatment often continues into adulthood. Amphetamine is commonly used for the treatment of ADHD and is available by prescription as either the d-enantiomer or a mixture of enantiomers. Although used for many years, there are no data available to describe the excretion profile of amphetamine and its enantiomers following repeated use of the drug. As a result, medical review officers (MROs) and forensic toxicologists have no direct evidence to base their decisions on when it comes to evaluation of use of these drugs. The current study was designed to determine the concentration and enantiomer excretion profile following repeated daily administration of mixed enantiomers of amphetamine. Twenty milligrams of Adderall was administered daily to five healthy subjects with all subsequent ad lib urine samples collected for at least five days following administration of the five-dose regimen. Adderall is a 3:1 mixture of d- and l-enantiomers of amphetamine salts and represents the mixed enantiomer proportion of amphetamine available in the United States through pharmaceutical channels. Peak amphetamine concentrations ranged from 5739 to 19,172 ng/mL. Samples containing > or = 500 ng/mL amphetamine (the administrative cutoff for a positive result by gas chromatography-mass spectrometry) were seen up to 60:15 (h:min) following administration of the last dose. Enantiomer analysis showed the d-enantiomer to be in excess of the l-enantiomer for as long as the drug was administered. After administration of the last dose of drug, the proportion of l-enantiomer increased over time. Not all samples that contained > or = 500 ng/mL total amphetamine were positive when tested by immunoassay because of the differing cross-reactivity of the enantiomers. This study provides the first description of the excretion of amphetamine following repeated administration of Adderall. The presence of the l-enantiomer separates this drug from other formulations composed of only the d-enantiomer (i.e., Dexedrine and much illicit amphetamine), thus readily differentiating them from Adderall use. Some illicit and medicinal amphetamine is, however, a mixture of amphetamine enantiomers. Because the enantiomers are metabolized at different rates, their proportion offers the opportunity to describe excretion versus time. Coupling this data with drug concentration makes it possible for forensic toxicologists and MROs to come to an informed decision regarding the involvement of this drug in a positive drug test result.
Clinical Research Division, Wilford Hall Medical Center, Lackland AFB, Texas.
3,4-Methylenedioxymethamphetamine (MDMA), a commonly encountered drug of abuse, has been shown in a variety of studies to cause neurotoxic effects. Because MDMA itself is not neurotoxic, identifying the potential neurotoxic metabolite(s) was of significant importance. Evaluation of urine and plasma concentrations of MDMA and three of its main metabolites, 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxyamphetamine (HMA), and 4-hydroxy-3-methoxymethamphetamine (HMMA), following administration of a neurotoxic dose (20 mg/kg) to male Dark Agouti rats was accomplished. Currently there are no data available describing urine and plasma concentrations of MDMA and these metabolites over a period of 7 days. The rats received a single 20 mg/kg i.p. dose of MDMA. Blood and urine samples were collected prior to administration and at 2, 4, 8, 12, 16, 20, 24, 48, 96, and 168 h following drug administration. Plasma and urine samples were extracted using solid-phase extraction, derivatized with N-methyl-bis(trifluoroacetamide), then analyzed using gas chromatography-mass spectrometry. Urine samples showed peak concentrations of MDMA at 4 h, MDA at 8 h, HMMA at 12 h, and HMA at 16 h post dose. MDMA and its metabolites were detectable (limit of detection 25 ng/mL) in the urine for up to 168 h post dose. Plasma samples showed mean peak concentrations of MDMA and MDA at 2 h post dose and HMMA at 4 h. Although the highest mean concentration of HMA was seen at 24 h post dose, variability between sample results for this time point was significant. No detectable levels of MDMA, MDA, HMA, and HMMA (LOD 10 ng/mL) were found in plasma at 96 and 168 h post dose.
Department of Clinical Laboratory Sciences, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
One of the 14 different drugs known to be metabolized to methamphetamine and/or amphetamine is famprofazone, a component in the multi-ingredient formulation Gewodin. Because of its conversion to methamphetamine and amphetamine, which can result in positive drug-testing results, the excretion pattern of these metabolites is critical for proper interpretation of drug-testing results. Multiple doses of famprofazone were administered to healthy volunteers with no previous history of methamphetamine, amphetamine, or famprofazone use. Following administration, urine samples were collected ad lib for nine days, and pH, specific gravity, and creatinine values were determined. To determine the methamphetamine and amphetamine excretion profile, samples were extracted, derivatized, and analyzed by gas chromatography-mass spectrometry (GC-MS). Peak concentrations of methamphetamine ranged from 5327 to 14,155 ng/mL and from 833 to 3555 ng/mL for amphetamine and were reached between 12:22 and 48:45 h post initial dose. There were 15-19 samples per subject that were positive under HHS testing guidelines, with the earliest at 03:37 h post initial dose and as late as 70:30 h post last dose. Methamphetamine and amphetamine were last detected (LOD > or = 5 ng/mL) up to 159 h and 153 h post last dose for methamphetamine and amphetamine, respectively. GC-MS was also used to determine the enantiomeric composition of methamphetamine and amphetamine. This analysis revealed both enantiomers were present in a predictable pattern.
Graduate Program in Clinical Laboratory Sciences, Department of Clinical Laboratory Sciences, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA
There are a several drugs that lead to the production of methamphetamine and/or amphetamine in the body which are subsequently excreted in the urine. These drugs raise obvious concerns when interpreting positive amphetamine drug testing results. Famprofazone is an analgesic found in a multi-ingredient medication (Gewodin) used for pain relief. Two Gewodin tablets (50 mg of famprofazone) were administered orally to healthy volunteers with no history of amphetamine, methamphetamine, or famprofazone use. Following administration, urine samples were collected ad lib for up to six days, and pH, specific gravity, and creatinine values were determined. In order to determine the quantitative excretion profile of amphetamine and methamphetamine, samples were extracted using liquid-liquid extraction, derivatized with heptafluorobutyric anhydride, and analyzed by gas chromatography-mass spectrometry (GC-MS). The ions monitored were 91, 118, 240 for amphetamine and 254, 210, 118 for methamphetamine. Amphetamine-d(6) and methamphetamine-d(11) were used as internal standards. Peak concentrations for amphetamine ranged from 148 to 2271 ng/mL and for methamphetamine 615 to 7361 ng/mL. Concentrations of both compounds peaked between 3 and 7 h post-dose. Amphetamine and methamphetamine could be detected (limit of detection = 5 ng/mL) at 121 and 143 h post-dose, respectively. Using a cutoff of 500 ng/mL, all subjects had individual urine samples that tested positive. One subject had 14 samples above the cutoff with the last positive being detected over 48 h post-dose. The profile of methamphetamine and amphetamine enantiomers was also determined using liquid-liquid extraction, derivatization with N-trifluoroacetyl-l-prolyl chloride and analysis by GC-MS. Data showed the famprofazone metabolites amphetamine and methamphetamine to be both d- and l-enantiomers. The proportion of l-methamphetamine exceeded that of its d-enantiomer from the first sample collected. Initially, the proportion was approximately 70% l-methamphetamine and this proportion increased over time. Amphetamine results showed l- and d-amphetamine were virtually the same in the early samples with the proportion of l-amphetamine increasing as time progressed. Forensic interpretation of drug testing results is a challenging critical part of forensic drug testing area because of the potential repercussions the results found may have on an individual's life. The finding of each enantiomers by itself differentiates famprofazone use from the most commonly abused form of methamphetamine and all medicinal methamphetamine available in the U.S., which is either d-methamphetamine (prescription medication) or l-methamphetamine (Vicks inhaler). Coupling this information with the concentrations of amphetamine and methamphetamine helps to determine the potential for use of this drug.
59th Clinical Research Squadron, Lackland AFB, TX 78236-5319, USA. sandra.valtier@59mdw.whmc.af.mil
Stealth is an adulterant that is advertised as not only preventing a positive drug test in urine, but also to be undetectable by currently available adulteration testing. It has previously been described as a peroxidase and peroxide that is added to urine for the sole purpose of preventing a positive drug test. The product was found to have a significant impact on the ability to detect several drugs of abuse, however, detecting the presence of the adulterant in urine had not yet been reported. A simple procedure to detect the presence of this adulterant in urine was developed. This simple color test procedure using commercially available reagents commonly used in clinical laboratories is based on the use of a chromogen to detect the peroxidase reaction in urine samples. If Stealth is present in the urine, the test sample will show an immediate color change from clear to dark brown. This qualitative test can also be adapted for use with a spectrophotometer or autoanalyzer.
Academy of Health Sciences, MCCS-HMP PA Branch, Fort Sam Houston, Texas 78234-6138.
Amphetamine remains a widely abused drug throughout the world. It is also used therapeutically for weight loss, narcolepsy, and attention deficit disorder with hyperactivity (ADHD). ADHD has grown dramatically recently both in terms of diagnosis and treatment. Increasingly, older individuals are diagnosed and treated for ADHD, and treatment often continues into adulthood. Of the available treatments for ADHD, Adderall is widely prescribed. Despite its widespread use, there are no published data regarding the expected amphetamine excretion profile following its use. This is problematic because, in this case, medical review officers (MRO) and forensic toxicologists are asked to assess results in terms of use pursuant to valid medical prescription without specific data on which to base a sound decision. To address this situation, a study to determine the concentration and enantiomer composition of amphetamine excretion following administration of Adderall was undertaken. Adderall (20 mg) was administered to five healthy subjects with all subsequent ad lib urine samples (total urine void) collected for seven days. Adderall is a 3:1 mixture of d- and l-enantiomers of amphetamine salts. Peak amphetamine concentrations ranged from 2645 to 5948 ng/mL. Samples containing > 500 ng/mL of amphetamine (the administrative cutoff for a positive result by gas chromatography-mass spectrometry) were seen up to 47:30 h post dose. The number of samples that contained amphetamine concentrations of > 500 ng/mL ranged among individuals from 7 to 13. As anticipated, analysis showed the d-enantiomer to be in excess of the l-enantiomer, with the proportion of l-enantiomer increasing over time. Because of the mixture of enantiomers, not all samples that contained > 500 ng/mL of amphetamine were positive when tested by immunoassay. The drug concentration profiles were quite variable within and between subjects because of dilution and fluctuations in pH of the samples. These results are the first to describe the excretion of amphetamine following administration of Adderall. The presence of the l-enantiomer separates this drug from other preparations of the drug that are composed of only the d-enantiomer (i.e., dexedrine and much illicit amphetamine), thus readily differentiating them from Adderall use. Some illicit and medicinal amphetamine is, however, a mixture of amphetamine enantiomers. Because the enantiomers are metabolized at different rates, their proportion offers the opportunity to describe excretion versus time. Coupling this data with drug concentration makes it possible for forensic toxicologists and MROs to come to an informed decision about the involvement of this drug in a positive drug test result. Using the combination of enantiomer composition and quantitative data will allow MROs and forensic toxicologists to better assess the use of this drug from abuse of amphetamine.
Graduate Program in Clinical Laboratory Sciences, Department of Clinical Laboratory Sciences, University of Texas Health Science Center, San Antonio, Texas 78229-3900.
There are a several drugs that lead to the production of methamphetamine and/or amphetamine in the body which are subsequently excreted in the urine. These drugs raise obvious concerns when interpreting positive amphetamine drug testing results. Famprofazone is an analgesic found in a multi-ingredient medication (Gewodin(R)) used for pain relief. Two Gewodin tablets (50 mg of famprofazone) were administered orally to healthy volunteers with no history of amphetamine, methamphetamine, or famprofazone use. Following administration, urine samples were collected ad lib for up to six days, and pH, specific gravity, and creatinine values were determined. In order to determine the quantitative excretion profile of amphetamine and methamphetamine, samples were extracted using liquid-liquid extraction, derivatized with heptafluorobutyric anhydride, and analyzed by gas chromatography-mass spectrometry (GC-MS). The ions monitored were 91, 118, 240 for amphetamine and 254, 210, 118 for methamphetamine. Amphetamine-d6 and methamphetamine-d11 were used as internal standards. Peak concentrations for amphetamine ranged from 148 to 2271 ng/mL and for methamphetamine 615 to 7361 ng/mL. Concentrations of both compounds peaked between 3 and 7 h post-dose. Amphetamine and methamphetamine could be detected (limit of detection = 5 ng/mL) at 121 and 143 h post-dose, respectively. Using a cutoff of 500 ng/mL, all subjects had individual urine samples that tested positive. One subject had 14 samples above the cutoff with the last positive being detected over 48 h post-dose. The profile of methamphetamine and amphetamine enantiomers was also determined using liquid-liquid extraction, derivatization with N-trifluoroacetyl-l-prolyl chloride and analysis by GC-MS. Data showed the famprofazone metabolites amphetamine and methamphetamine to be both d- and l-enantiomers. The proportion of l-methamphetamine exceeded that of its d-enantiomer from the first sample collected. Initially, the proportion was approximately 70% l-methamphetamine and this proportion increased over time. Amphetamine results showed l- and d-amphetamine were virtually the same in the early samples with the proportion of l-amphetamine increasing as time progressed. Forensic interpretation of drug testing results is a challenging critical part of forensic drug testing area because of the potential repercussions the results found may have on an individual's life. The finding of each enantiomers by itself differentiates famprofazone use from the most commonly abused form of methamphetamine and all medicinal methamphetamine available in the U.S., which is either d-methamphetamine (prescription medication) or l-methamphetamine (Vicks inhaler). Coupling this information with the concentrations of amphetamine and methamphetamine helps to determine the potential for use of this drug.
Franklin County Coroner's Office, Columbus, OH 43201, USA. jfwyman@franklincountyohio.gov
Methamphetamine was detected in a 77-year-old male who had a history of congestive heart failure. Using a modification of a previously reported method, trifluoroacetyl-l-prolyl chloride was used to derivatize sympathomimetic amines to allow separation and identification of individual enantiomers. The l-enantiomer of methamphetamine and a trace amount of l-amphetamine were found in blood and urine specimens from this case. Further investigation revealed the decedent had bronchial asthma and regularly used a Vicks Inhaler, which contains l-methamphetamine as the active ingredient.
Interservice Physician Assistant Program, Army Medical Department Center and School, Department of Medical Sciences, 3151 Scott Road, Fort Sam Houston, TX 78234-6138, USA.
Although the first physician assistant (PA) program was born at a civilian academic institution, the impact of the military was immediately obvious as evidenced by the entire first class of PA students being Vietnam veteran Navy Corpsmen. Following initiation of the PA profession, the armed services established their own PA training programs that were eventually consolidated into a single interservice program in 1996. The mission of the Interservice PA Program is to produce high-quality PAs prepared to provide medical care in not only the traditional clinical arena but in the more unique situations seen in both peacetime and wartime military settings. PAs must complete an approved formal training program encompassing didactic and clinical training and pass a national certification examination to be licensed to practice. Pass rates are a key measure of the quality of a training program. We compared the national certification examination pass rates for our program with those of accredited civilian programs. Graduates of our program had a significantly higher pass rate and higher average scores than their civilian counterparts. These results are due to the strength of the program and faculty as well as the considerable hard work and dedication of the students who are drawn from a community that is, in many ways, non-traditional compared with other PA programs. These results demonstrate that the military training of PAs continues to provide high-quality health care providers who perform above their civilian-trained counterparts.
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Kristen M Bailey,
David J Clay,
Myron A Gebhardt,
Matrina J Schmidt,
Nabila A Haikal,
James C Kraner
Office of the Chief Medical Examiner, Charleston, West Virginia, USA. Kristen.M.Bailey@wv.gov
Cocaine is one of the most widely abused drugs and one that is frequently encountered in forensic toxicology laboratories. Most often, the detection of cocaine would lead toxicologists and forensic pathologists to believe that the drug was used illicitly; however, cocaine is an effective local anesthetic and vasoconstrictor and is used clinically in surgeries of the eye, ear, nose, and throat. Therefore, it is important to note that the presence of cocaine and its metabolites in forensic samples cannot always be attributed to abuse and that a thorough investigation and review of medical records is warranted before an informed conclusion can be made. In this case report, a 54-year-old male died three days after an altercation in which he suffered multiple injuries. In addition to natural disease and injuries documented at autopsy, cocaine and its metabolites were detected in the decedent's urine, and a review of surgical records showed that earlier on the day of death, he was administered cocaine clinically during a procedure to repair nasal bone fractures. If not for this comprehensive investigation and review of surgical records, the assumption of cocaine abuse might have otherwise been made and the cause and manner of death incorrectly established.
Department of Physical and Analytical Chemistry, Uppsala University, BMC Box 599, SE-751 24 Uppsala, Sweden.
Traditionally, the choice of acid/base additives used in chiral preparative chromatography has not been considered very important. However, it was recently demonstrated that strongly adsorbing additives can result in the most unexpected enantiomer band shapes in modern chiral preparative chromatographic systems. In the present study we demonstrate that, depending on the choice of additive, it is actually possible to obtain the following four binary band-shape compositions when a racemic mixture is injected:(i) anti-Langmuir/anti-Langmuir,(ii) anti-Langmuir/Langmuir,(iii) Langmuir/Langmuir and (iv) Langmuir/anti-Langmuir. Further, we made an advanced numerical investigation, in order to ascertain which one of the four band-shape compositions, is the most favourable one in preparative batch chromatography of a racemic mixture. We found that if the target for purification is either the first eluting enantiomer or both ones, the traditional Langmuir/Langmuir band-shape composition should be chosen. But, if only the second eluting enantiomer is to be purified the optimal situation is the anti-Langmuir/Langmuir band-shape composition. Thus, it was concluded that the best choice of additive depends on which enantiomer is of interest and it is useful to perform a thorough additive screening to find the optimal additive, giving the most advantageous peak shape composition and accordingly the best process performance for a particular separation problem.
School of Nursing and Midwifery, Faculty of Health Sciences, Curtin University of Technology, GPO Box U1987, Perth, Western Australia, 6845, Australia. anne.bartu@health.wa.gov.au
AIMS: To investigate the transfer of amphetamines into breast milk following their recreational use and estimate drug exposure for the breastfed infant. METHODS: Two breastfeeding mothers who were occasional recreational users of intravenous amphetamines were studied. A urine sample was collected 4 h after dose, and milk samples were collected over 24 h. Drug in urine was qualitatively identified by gas chromatography-mass spectrometry and quantification in milk was by high-performance liquid chromatography. Absolute infant dose via milk was estimated. RESULTS: The urines contained predominantly methylamphetamine together with smaller amounts of amphetamine. In the 24 h after dose, average concentrations in milk were 111 microg l(-1) and 281 microg l(-1) for methylamphetamine and 4 microg l(-1) and 15 microg l(-1) for amphetamine in cases 1 and 2, respectively. Absolute infant doses for methylamphetamine plus amphetamine (as methylamphetamine equivalents) were 17.5 microg kg(-1) day(-1) and 44.7 microg kg(-1) day(-1), respectively, for cases 1 and 2. CONCLUSION: These limited data suggest that breastfeeding should be withheld for 48 h after recreational amphetamine use.
University of Huddersfield, Department of Chemical and Biological Sciences, Queensgate, Huddersfield HD1 3DH, UK; University of Glamorgan, Sustainable Environment Research Centre, Faculty of Health, Sport and Science, Pontypridd CF37 1DL, UK.
Pharmaceuticals and recently also illicit drugs have been recognised as emerging environmental contaminants due to their potential environmental impact: frequent occurrence, persistence and risk to aquatic life and humans. This manuscript is part one of the two-part study aiming to provide a better understanding and application of environmental data not only for environmental aims but also to meet forensic objectives. An attempt to use wastewater data is made in order to verify patterns of the usage of drugs (in particular illicit) in local communities. The average usage of cocaine in South Wales was estimated at .9 g day(-1) 1000 people(-1), which equals 1 tonne of this drug used or disposed of to sewage annually in Wales. The calculated usage of amphetamine denoted 2.5 g day(-1) 1000 people(-1) and is suspected to be an overestimate. Because no analysis of enantiomers of amphetamine was undertaken, no distinction between amphetamine's legal and illicit usage could be made.
Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. sbarker@vetmed.lsu.edu
Beginning in 2004, the horseracing industry experienced an epidemic of drug positives for the amphetamine-like drug aminorex. Investigation of the therapeutic treatment of the horses called positive for this drug suggested that its source was from the administration of the anthelmintic levamisole. This study examines the urine concentrations of aminorex as a function of time following administration of synthetic, racemic aminorex. Confirmation of the presence of aminorex in urine samples from the horses known to be treated with levamisole is also presented as are data concerning the concentrations of aminorex in positives called from the field and the corresponding concentrations of levamisole found in the same samples. Furthermore, this study illustrates that the chiral isomer distribution of aminorex found in samples from the field is significantly different from that arising from the administration of synthetic, racemic aminorex and is similar to that observed from aminorex arising from levamisole administration. An examination of the chiral isomer distribution of aminorex and a determination of the presence of levamisole in a sample may be used to assess the source of an aminorex positive, distinguishing it from an intentional synthetic, racemic aminorex administration. The role of levamisole in aminorex formation is also discussed.
This article details the rapid extraction of amphetamines from oral fluid using low specimen volume, low sorbent bed mass, and fast gas chromatography with mass selective detection. The collection of a known amount of sample volume coupled with high percentage recovery of drug from the collection pad has allowed oral fluid to be increasingly employed as the specimen of choice for the detection of drug use in various applications. Additionally, low specimen volume for confirmation is required, so that adequate test volume remains for second analysis in case of batch failure or for testing at a different laboratory facility. The extracts were prepared using low bed mass sorbent, so less conditioning, washing, and elution solvent further reduced the overall cost of sample preparation. The limits of quantitation for the assay were 25 ng/mL; the intraday precision of the assays (n = 5) ranged from .3 to 3.99%; interday precision ranged from .72 to 4.6% for the amphetamine class. The percentage recovery of the drugs from the collection pads ranged from 85.4 to 89.1%(n = 6). The process lends itself to widely available automated processing instrumentation and significantly increases the efficiency of laboratories providing high-volume oral fluid analysis for drugs of abuse.
An 18-year-old man with attention-deficit-hyperactivity disorder (ADHD) was prescribed varenicline for smoking cessation. He quit smoking after 1 week of therapy and remained smoke free for the next 17 days. During that time, he had also been taking amphetamine-dextroamphetamine (Adderall) on work days for his ADHD. Because his supply of amphetamine-dextroamphetamine was diminishing, he took only half (30 mg every morning) of his prescribed dosage from days 4-12 of varenicline therapy. He further reduced his dosage to 15 mg every morning on days 13 and 14 of varenicline therapy, and his supply of amphetamine-dextroamphetamine was depleted on day 15. On day 23 of varenicline therapy, he received and filled a new prescription for amphetamine-dextroamphetamine and resumed his prescribed dosage (30 mg twice/day). He began smoking again within 48 hours. Rechallenge with varenicline while the patient continued to receive amphetamine-dextroamphetamine yielded similar results. Data suggest that addition of amphetamine to varenicline may negate the partial agonism of varenicline, resulting in elimination of the smoking-cessation aid's benefits. Other potential mechanisms for the drug interaction may also exist. Thus, varenicline may not aid smoking cessation in patients undergoing treatment with amphetamine and amphetamine-like drugs.
National Public Health Institute, Drug Research Unit, Mannerheimitie 166, FI-00300 Helsinki, Finland.
This study investigated amphetamine concentrations in both oral fluid and whole blood samples of persons suspected of driving under the influence of drugs. The data for the study were obtained from 153 cases. The mean volume of oral fluid collected with the Intercept((R)) oral fluid collection device was 224 microL. Because of the small sample volume of oral fluid, the results of the amphetamine concentrations in oral fluid were not used in the calculations for 39 cases. The total number of cases positive for amphetamine in oral fluid was 100 out of 114. In seven cases the oral fluid sample was positive (cutoff 25 microg/L), even though the whole blood sample was negative (cutoff 20 microg/L). All of the cases found positive in whole blood (n = 93) were also positive in oral fluid. Oral fluid would therefore be well suited as a testing matrix for amphetamine when driving under the influence is suspected. The results nevertheless indicated that the cutoff used for amphetamine in oral fluid (i.e., 25 microg/L) could be higher to correspond to the window of detection given by the level of 20 microg/L in whole blood.
Elias Miranda-G,
Monserrat Sordo,
Ana M Salazar,
Claudia Contreras,
Leoncio Bautista,
Aurora E Rojas García,
Patricia Ostrosky-Wegman
Instituto de Investigaciones Biomédicas and Facultad de Química, Universidad Nacional Autónoma de México, México DF; Centro de Diagnóstico e Investigación en Medicina Preventiva en el Transporte, SCT, México.
Amphetamine, a CYP2D6 substrate, is widely used by truck drivers, and the extent to which different people metabolize the drug has only been determined in an isolated or reduced number of samples. A gas chromatography-mass spectrometry method is implemented to simultaneously determine amphetamine, methamphetamine, and hydroxyamphetamine in the urine of drug users. This method is a useful contribution to a well-established field. The main improvements are the use of liquid-liquid extraction, the trapping of the amphetamines as their hydrochloride salt, as a solution to the volatility of these analytes, and its application to assess the CYP2D6 metabolic phenotype of amphetamine users, which is innovative. Calibration curves ranged from 125 to 1000 ng/mL and had an r(2) greater than .99. The validation data (precision, accuracy, and recovery) shows the reproducibility and selectiveness of the method. The method is applied to determine the metabolic ratio (MR) in 121 urine specimens of federal highway drivers who underwent random mandatory roadside testing for drugs. The statistical analysis of the MR shows the presence of three different groups, which according to the established groups for CYP2D6 and the amount of the drug metabolized, are classified into extensive metabolizers (EM), intermediate metabolizers (IM), and poor metabolizers (PM). The biological consequences of these differences in amphetamine metabolism, such as impaired driving, a risk to develop Parkinson's disease, or an addiction, need to be further studied.
