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Methadone is a potent synthetic opioid used for treatment of opioid dependence and chronic pain. Florida Department of Law Enforcement data were analyzed to examine trends in deaths related to or caused by methadone and/or heroin between 2001-2006. Results demonstrated that mortalities associated with methadone use increased steadily as mortalities associated with heroin decreased steadily. Though useful in the treatment of opioid dependence and chronic pain, methadone possesses high abuse potential and documented mortality risks. Treatment with methadone, for both pain and opioid dependence, should be preceded by an abuse liability evaluation. Attempts to minimize diversion should be implemented.

Despite the fact that blood and urine are the most commonly encountered specimens, alternative body fluids have gained significant importance in the fields of forensic and clinical toxicology, doping control, workplace drug testing, and drug treatment programs. Although alternative specimens may offer distinct advantages over their conventional counterparts, they can also present a number of analytical and interpretive challenges. Alternative body fluids are reviewed in terms of their relative merits, uses, analysis, and interpretive value.

Background Immunomodulatory effects in humans of Δ9−Tetrahydrocannabinol (THC), the psychoactive component of marijuana are controversial. Tissue factor (TF), the activator of the extrinsic coagulation cascade, is increased on circulating activated monocytes and is expressed on microvesicles released from activated monocytes during inflammatory conditions, which perpetuate coagulopathies in a number of diseases. In view of the increased medicinal use of marijuana, effects of THC on human monocytes and monocyte-derived microvesicles activated by lipopolysaccharide (LPS) were investigated. Findings Peak levels of TF procoagulant activity developed in monocytes or microvesicles 6 h following LPS treatment and were unaltered by THC. After 24 h of LPS stimulation, TF activity declined in control-treated or untreated cells and microvesicles, but persisted with THC treatment. Peak TF protein occurred within 6 h of LPS treatment independent of THC; by 24 h, TF protein declined to almost undetectable levels without THC, but was about 4-fold greater with THC. Steady-state TF mRNA levels were similar up to 2 h in the presence of LPS with or without THC, while 10-fold greater TF mRNA levels persisted over 3–24 h with THC treatment. Activation of MAPK or NF-κB pathways was unaltered by THC treatment and inflammatory cytokine IL-6 levels were unchanged. In contrast, TNF and IL-8 levels were enhanced by 20–50 %. Conclusions THC enhances TF expression in activated monocytes resulting in elevated procoagulant activity. Marijuana use could potentiate coagulopathies in individuals with chronic immune activation such as HIV-1 infection or inflammatory bowel disease.

Enhanced reinforcing effects of nicotine during adolescence appear to contribute to the rapid development of dependence in this age group. However, the contribution of nicotine withdrawal to dependence in adolescents is unclear.We compared motivational and somatic signs of nicotine withdrawal in adolescent and adult rats.In experiment 1, motivational signs of nicotine withdrawal were compared using intracranial self-stimulation procedures after administration of mecamylamine (1.5 mg/kg, i.p.) in adolescent and adult rats made dependent on nicotine (9 mg/kg/day). Somatic signs of withdrawal were compared in two experiments using various doses of nicotine (adolescent doses: 0, 1.6, 3.2, 4.7 mg/kg/day; adult doses: 0, 1, 2.1, 3.2 mg/kg/day, expressed as nicotine base) to produce dependence and one dose of mecamylamine (1.5 mg/kg, i.p.) to precipitate withdrawal (experiment 2) and in a subsequent experiment, using various doses of mecamylamine (0, 0.75, 1.5, 3.0 mg/kg, i.p.) to precipitate withdrawal and a dose of nicotine (adolescent dose: 4.7 mg/kg/day; adult dose: 3.2 mg/kg/day) that produced equivalent nicotine blood levels in these age groups (experiment 3).Adolescents did not display the decreases in brain reward function observed in adults experiencing withdrawal, and displayed fewer somatic signs of nicotine withdrawal relative to adults regardless of the dosing procedure used.The negative effects of nicotine withdrawal are lower during adolescence relative to later periods of development. Both the enhanced rewarding effects and the diminished nicotine withdrawal likely contribute to the rapid development of nicotine use during adolescence.

We hypothesize that aerosolization of anesthetics administered intravenously to patients in the operating room may be an unintended source of exposure to physicians. This may lead to inadvertent sensitization, which is associated with an increased risk for developing addiction. This may contribute to the over-representation of certain specialties among physicians with addiction. We retrospectively reviewed the de-identified demographic information of all licensed physicians treated for substance abuse in the State of Florida since 1980, to determine if medical specialty was associated with addiction in this group of individuals. Then, to identify the potential for exposure, two mass spectrometry assays were developed to detect two intravenously administered drugs, fentanyl and propofol, in air. Since 1980, 7.6% of licensed Florida physicians underwent treatment for addiction. Addiction in anesthesiologists was higher than expected. Opiate abuse was greater in anesthesiologists and surgeons compared to other specialties. Aerosolized fentanyl was detected in the air of the cardiothoracic operating room, in patients' expiratory circuits, and in the headspace above sharps boxes, but not in adjoining hallways. Aerosolized propofol was detected in the expirations of a patient undergoing transurethral prostatectomy. While access and stress may place anesthesiologists and surgeons at greater risk for substance abuse, an additional risk factor may be unintended occupational exposure to addictive drugs. This report provides preliminary evidence of detection of aerosolized intravenous anesthetics using two newly developed analytical methods. We conclude that the potential exists for chronic exposure to low levels of airborne intravenously administered drugs. Further studies are under way to determine the significance of this exposure.

Anaphylactic drug reactions are rare and often serious events. The Botulinum toxin A, marketed as BOTOX, was recently approved by the Food and Drug Administration for cervical dystonia and glabellar wrinkles, after its approved use and success with blepharospasm, strabismus, and disorders of the 7th cranial nerve. It has been well received due to its efficacy in improving facial lines. This case report documents the first death associated with a Botox-lidocaine mixture given to a woman for chronic neck and back pain. Based on the medical records, autopsy, and laboratory findings, the cause of death was determined to be anaphylaxis to the Botox-lidocaine mixture. The history, indications, off-label uses and possible future applications of Botox are reviewed as well as the uses and complications of lidocaine. Although the anaphylaxis cannot be definitively proven to be due to Botox alone, this case warns of an adverse reaction related to Botox, a drug that is rapidly expanding in range of use as well as increased usage.

A letter to the editor is presented in response to the article "Opioid overdose deaths and Florida's crackdown on pill mills," by A. Kennedy-Hendricks, M. Richey, E. E. McGinty and colleagues in a 2016 issue.

Objective: We developed and validated an analytical method for quantifying 25-hydroxyvitamin D2 (25OHD2) and 25-hydroxyvitamin D3 (25OHD3) in serum and plasma. Methods: Samples, pretreated with zinc sulfate and methanol, were extracted with hexane. Separation was achieved via UHPLC and 25OHD quantification was accomplished by a triple quadrupole mass spectrometer. Results: Imprecision was 3.6–15.1%CV and bias 88.0–126.0%. Extraction efficiency was 76.5–110.5%, whereas the matrix effect ranged from −46.7 to −32.0%. The method was applied to authentic specimens. The results showed no significant difference between serum and plasma; strong correlation with paired values from an external laboratory; and analyte stability for 15 days. Conclusion: This method provides reliable and accurate measurement of 25OHD for use in clinical practice.

Urine drug testing (UDT) services are provided by a variety of clinical, forensic, and reference/specialty laboratories. These UDT services differ based on the principal activity of the laboratory. Clinical laboratories provide testing primarily focused on medical care (eg, emergency care, inpatients, and outpatient clinics), whereas forensic laboratories perform toxicology tests related to postmortem and criminal investigations, and drug-free workplace programs. Some laboratories now provide UDT specifically designed for monitoring patients on chronic opioid therapy. Accreditation programs for clinical laboratories have existed for nearly half a century, and a federal certification program for drug-testing laboratories was established in the 1980s. Standards of practice for forensic toxicology services other than workplace drug testing have been established in recent years. However, no accreditation program currently exists for UDT in pain management, and this review considers several aspects of laboratory accreditation and certification relevant to toxicology services, with the intention to provide guidance to clinicians in their selection of the appropriate laboratory for UDT surveillance of their patients on opioid therapy.

Forensic toxicology is the study and practice of the application of toxicology to the purposes of the law. The internet provides abundant web-sites and resources for the practicing forensic toxicologist and those interested in the field of forensic toxicology. This review includes a description of web-sites, databases of toxicological and analytical data, and web-based journals, forums and mailing lists.

To understand the mortality patterns among drug users and potential risk factors, we evaluated drug-related deaths reported to the Florida Medical Examiners Commission from 2001 to 2013, by substances, demographics, and manner of death. The annual drug-related fatalities increased by 57% from 2001 to 2013 (total n = 100,882); 51.8% were accidental, 7.9% homicide, 18.6% natural, and 19.6% suicide. The different manners of death exhibited distinct demographic profiles and drug composition. The gender gap was more prominent in homicide. Age ≥55 years was more closely associated with natural death and suicide. Age

BACKGROUND: In Florida, oxycodone-caused deaths declined substantially in 2012. Multiple important law enforcement, pharmaceutical, policy, and public health actions occurred concurrently, including implementation of a statewide Prescription Drug Monitoring Program (PDMP). The effects of the PDMP on oxycodone-caused mortality in Florida were evaluated. METHODS: A time-series, quasi-experimental research design with autoregressive integrated moving average (ARIMA) statistical models, including internal and external covariates. Data included 120 repeated monthly observations. Monthly counts of oxycodone-caused deaths, obtained from the Florida Medical Examiners Commission (MEC) was the outcome variable. Models included market-entry of tamper-resistant oxycodone HC1 controlled release tablets (OxyContin(®)), enforcement crackdowns (Operation Pill Nation), and regulation by FL House Bill 7095, measured by the monthly count of Florida pain management clinics closed. Two approaches were used to test the PDMP's hypothesized effect: (1) a binary indicator variable (0=pre-implementation, 1=post-implementation), and (2) a continuous indicator consisting of the number of PDMP queries by health care providers. RESULTS: Oxycodone-caused mortality abruptly declined 25% the month after implementation of Florida's PDMP (p=0.008). The effect remained after integrating other related historical events into the model. RESULTS indicate that for a system-wide increase of one PDMP query per health care provider, oxycodone-caused deaths declined by 0.229 persons per month (p=0.002). CONCLUSIONS: This is the first study to demonstrate that the PDMP had a significant effect in reducing oxycodone-caused mortality in Florida. RESULTS have implications for national efforts to address the prescription drug epidemic. Language: en

This study investigated the disposition patterns of cocaine and opiates into hair and fingernail specimens collected from 8 volunteers enrolled in a 10-week inpatient clinical study. All subjects were African-American males with a confirmed drug use history. Scalp hair and fingernail scrapings were collected weekly throughout the course of the study. Head hair was collected from the posterior vertex region, and fingernail scrapings were collected along the entire ventral surface of the nail plate. The specimens were introduced to successive decontamination washes including an isopropanol wash and three phosphate buffer washes. All decontamination washes were collected and analyzed. All specimens were enzymatically digested prior to being subjected to solid-phase extraction and derivatization. Analyses were performed using electron impact gas chromatography-mass spectrometry. Analytes investigated included eight cocaine analytes and five codeine analytes. The limit of quantitation for all analytes ranged from 0.1 to 0.5 ng/mg for both matrices. Cocaine was present at the highest concentrations of any analyte in both hair and nail. Benzoylecgonine and ecgonine methyl ester were the primary metabolites in both matrices and were typically less than 15% of cocaine concentrations. Codeine was the only opiate analyte identified in either hair or nail. Observed drug disposition profiles were different for hair and nails. A significant dose-response relationship was observed for hair specimens. The mean peak concentrations in hair after low dosing were half the concentration observed after high-dose administration. Generally, no clear relationship was evident between nail drug concentrations and dose. Decontamination washes removed less than 20% of the total drug present in hair, but removed most of the drug concentrations (60-100%) in nail. This investigation demonstrated that higher concentrations of drug were found in the subjects' hair than in their fingernails and that cocaine was found in both matrices at a greater concentration than codeine. Although both hair and nail have similar physical and chemical properties and may share common mechanisms of drug incorporation, this clinical study suggests that there are distinct differences in their disposition profiles.

Sweat and urine specimens were collected from 44 methadone-maintenance patients to evaluate the use of sweat testing to monitor cocaine use. Paired sweat patches that were applied and removed weekly (on Tuesdays) were compared with 3-5 consecutive urine specimens collected Mondays, Wednesdays, and Fridays. All patches (N = 930) were extracted in 2.5 mL of solvent and analyzed by ELISA immunoassay (cutoff concentration 10 ng/mL); a subset of patches (N = 591) was also analyzed by gas chromatography-mass spectrometry (GC-MS) for cocaine, benzoylecgonine (BZE), and ecgonine methyl ester (EME) (cutoff concentration 5 ng/mL). Urine specimens were subjected to qualitative analysis by EMIT (cutoff 300 ng/mL) and subsets were analyzed by TDx (semiquantitative, LOD 30 ng/mL) and by GC-MS for cocaine (LOD 5 ng/mL). Results were evaluated to (1) determine the relative amounts of cocaine and its metabolites in sweat; (2) assess replicability in duplicate patches; (3) compare ELISA and GC-MS results for cocaine in sweat; and (4) compare the detection of cocaine use by sweat and urine testing. Cocaine was detected by GC-MS in 99% of ELISA-positive sweat patches; median concentrations of cocaine, BZE, and EME were 378, 78.7, and 74 ng/mL, respectively. Agreement in duplicate patches was approximately 90% by ELISA analysis. The sensitivity, specificity, and efficiency of sweat ELISA cocaine results as compared with sweat GC-MS results were 93.6%, 91.3%, and 93.2%, respectively. The sensitivity, specificity, and efficiency between ELISA sweat patch and EMIT urine results were 97.6%, 60.5%, and 77.7%, respectively. These results support the use of sweat patches for monitoring cocaine use, though further evaluation is needed.

A simple method for the direct analysis of gamma-hydroxybutyrate (GHB) from human urine is described. The method uses solid-phase extraction, liquid-liquid extraction, and silyl-derivatization, then gas chromatographic-mass spectrometric analysis using GHB-d6 as the internal standard. The method was linear from 5 to 500 mg/L, and coefficients of variation were less than 10%. Twenty-six urine specimens previously analyzed by an existing method were analyzed and yielded GHB concentrations ranging from 0 to 6100 mg/L; the results correlated between the two methods. Compared with existing methods, the method described here is superior because it is specific to GHB and can discriminate between GHB and gamma-butyrolactone.

Caffeine is the world's most popular drug and can be found in many beverages including tea. It is a psychostimulant that is widely used to enhance alertness and improve performance. This study was conducted to determine the concentration of caffeine in 20 assorted commercial tea products. The teas were brewed under a variety of conditions including different serving sizes and steep-times. Caffeine was isolated from the teas with liquid-liquid extraction and quantitated by gas chromatography with nitrogen-phosphorus detection. Caffeine concentrations in white, green, and black teas ranged from 14 to 61 mg per serving (6 or 8 oz) with no observable trend in caffeine concentration due to the variety of tea. The decaffeinated teas contained less than 12 mg of caffeine per serving, and caffeine was not detected in the herbal tea varieties. In most instances, the 6- and 8-oz serving sizes contained similar caffeine concentrations per ounce, but the steep-time affected the caffeine concentration of the tea. These findings indicate that most brewed teas contain less caffeine per serving than brewed coffee.

Recreational drug use continues to be prevalent in many social settings. These drugs are alleged to enhance sociability and liberate inhibitions, allowing the user to experience feelings of euphoria. This article reviews recreational drugs that have gained notoriety in the 1990s including gamma-hydroxybutyrate (GHB), flunitrazepam, and amphetamine analogues such as 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA). Topics discussed include history, drug use and misuse, clinical presentation and treatment, and laboratory analysis.

The disposition of methadone, its metabolites, and other illicit drugs of abuse was investigated in head hair samples collected from heroin users (N = 20) enrolled in an outpatient detoxification study. Hair samples were assayed for methadone, methadone primary metabolite (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, EDDP), methadone secondary metabolite (2-ethyl-5-methyl-3,3-diphenylpyrroline, EMDP), cocaine, phencyclidine, heroin, and 6-acetylmorphine. Hair samples were cut, washed, and incubated in methanol. The methanolic hair wash and incubation fractions were purified with solid-phase extraction and assayed by gas chromatography-mass spectrometry. Methadone, methadone metabolites, cocaine, and phencyclidine were assayed quantitatively, and other drugs were measured qualitatively. The number of positive results and the corresponding concentration ranges were as follows: methadone, 0-15.0 ng/mg (N = 18); EDDP, trace (N = 13); EMDP, trace (N = 1); cocaine, 0->40 ng/mg (N = 14); phencyclidine, 0-1.5 ng/mg (N = 2); heroin, positive (N = 3); and 6-acetylmorphine, positive (N = 4). These data suggest that testing hair for methadone, methadone metabolites, and other illicit drugs of abuse may be useful to drug-treatment specialists as a means of verifying drug-use history, monitoring compliance, and providing a broad measure of drug exposure.

Caffeine is the most widely consumed drug in the world with coffee representing a major source of intake. Despite widespread availability, various medical conditions necessitate caffeine-restricted diets. Patients on certain prescription medications are advised to discontinue caffeine intake. Such admonition has implications for certain psychiatric patients because of pharmacokinetic interactions between caffeine and certain anti-anxiety drugs. In an effort to abstain from caffeine, patients may substitute decaffeinated for caffeinated coffee. However, decaffeinated beverages are known to contain caffeine in varying amounts. The present study determined the caffeine content in a variety of decaffeinated coffee drinks. In phase 1 of the study, 10 decaffeinated samples were collected from different coffee establishments. In phase 2 of the study, Starbucks espresso decaffeinated (N=6) and Starbucks brewed decaffeinated coffee (N=6) samples were collected from the same outlet to evaluate variability of caffeine content of the same drink. The 10 decaffeinated coffee samples from different outlets contained caffeine in the range of 0-13.9 mg/16-oz serving. The caffeine content for the Starbucks espresso and the Starbucks brewed samples collected from the same outlet were 3.0-15.8 mg/shot and 12.0-13.4 mg/16-oz serving, respectively. Patients vulnerable to caffeine effects should be advised that caffeine may be present in coffees purported to be decaffeinated. Further research is warranted on the potential deleterious effects of consumption of "decaffeinated" coffee that contains caffeine on caffeine-restricted patients. Additionally, further exploration is merited for the possible physical dependence potential of low doses of caffeine such as those concentrations found in decaffeinated coffee.

The caffeine content of 10 energy drinks, 19 carbonated sodas, and 7 other beverages was determined. In addition, the variability of the caffeine content of Coca-Cola fountain soda was evaluated. Caffeine was isolated from the samples by liquid-liquid extraction and analyzed by gas chromatography with nitrogen-phosphorus detection. The caffeine concentration of the caffeinated energy drinks ranged from none detected to 141.1 mg/serving. The caffeine content of the carbonated sodas ranged from none detected to 48.2 mg/serving, and the content of the other beverages ranged from < 2.7 to 105.7 mg/serving. The intra-assay mean, standard deviation, and % coefficient of variation for the Coca-Cola fountain samples were 44.5, 2.95, and 6.64 mg/serving, respectively.

A novel, simple and economic liquid-liquid extraction method for isolating cocaine from urine was developed utilizing gas chromatography-mass spectrometry (GC-MS) for analysis and quantification. The use of a single nonpolar organic solvent allowed only nonpolar analytes to be extracted from the biological fluid, and consequently, no derivatization step was necessary before GC-MS analysis. Large numbers of specimens (60) can be extracted in approximately 3 h with this procedure. The method is highly precise (C.V.7%), accurate (98%), sensitive (limit of detection of 5 ng/ml) and has a mean recovery of 48.8%.

Caffeine is the world's most widely consumed drug with its main source found in coffee. We evaluated the caffeine content of caffeinated and decaffeinated specialty coffee samples obtained from coffee shops. Caffeine was isolated from the coffee by liquid-liquid extraction and analyzed by gas chromatography with nitrogen-phosphorus detection. In this study, the coffees sold as decaffeinated were found to have caffeine concentrations less than 17.7 mg/dose. There was a wide range in caffeine content present in caffeinated coffees ranging from 58 to 259 mg/dose. The mean (SD) caffeine content of the brewed specialty coffees was 188 (36) mg for a 16-oz cup. Another notable find is the wide range of caffeine concentrations (259-564 mg/dose) in the same coffee beverage obtained from the same outlet on six consecutive days.

Motor vehicle crashes are a leading cause of morbidity and mortality in the United States. Drivers with measurable quantities of potentially impairing illicit or prescription drugs in their body fluids are multiple times more likely to be involved in motor vehicle crashes than those without such drugs in their bodies. Drug-related impairment, however, cannot be inferred solely on the basis of the presence of drugs in biological fluids. Thus, for more than a quarter century, there has been a search for drug blood concentrations that are the equivalent of the 0.08 g/dL threshold for alcohol-impaired driving in the United States. We suggest that such equivalents are a mirage, and cannot be determined due to variable drug tolerance, lack of consistent relationships between drug blood concentrations and impairment, innumerable drug combinations and multiple other factors. Thus, while the idea of determining impairing drug concentrations is attractive, it is ultimately unattainable, and withholding drugged driving legislation pending the acquisition of such data is tantamount to a plan for inaction with regard to an important and growing public health and safety problem. We propose specific legislation to address alcohol- and drug-impaired driving in the United States.

The Mandatory Guidelines for Federal Workplace Drug Testing Programs require the use of gas chromatography-mass spectrometry (GC-MS) for the confirmation of presumptive positive urine specimens. This review focuses upon GC-MS methods developed specifically for forensic confirmation of amphetamine, methamphetamine, 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (THC-acid), benzoylecgonine, morphine, codeine and phencyclidine in urine for purposes of workplace drug testing. In addition, current laboratory issues pertaining to each drug class are reviewed. Generally, drug assays utilized either liquid-liquid or solid-phase extraction methods, derivatization if necessary, and GC-MS detection operating in the selected ion monitoring mode or by full scan acquisition.

Although many deaths occur annually from heroin intoxication, the presence of heroin has not been reported in postmortem tissues. Recognizing heroin's susceptibility to rapid chemical and metabolic hydrolysis, extraction procedures were developed for the efficient recovery of heroin, 6-acetylmorphine, and morphine from postmortem tissue utilizing solid-phase extraction coupled with gas chromatography/mass spectrometry. From heroin-related deaths, 21 sets of blood and urine specimens were collected. The mode of death in these cases was categorized as rapid, delayed, or undetermined. Compared with delayed deaths, rapid deaths were characterized by the following trends: higher mean concentrations of 6-acetylmorphine, free morphine, and total opiates in blood; a higher ratio of free morphine concentrations to total opiate concentrations in blood; lower mean concentrations of 6-acetylmorphine and morphine in urine; greater likelihood of 6-acetylmorphine detection in blood; and lesser likelihood of heroin detection in urine. The study also included analysis of multiple tissue specimens from two subjects who died of heroin intoxication. Heroin was identified in urine and injection-site tissue. Concentrations of 6-acetylmorphine in cerebrospinal fluid, spleen, and brain were substantially higher than in blood, liver, lung, and kidney. All specimens were positive for morphine. Heroin metabolites were detected in hair specimens. The identification of heroin and 6-acetylmorphine in biological tissues effectively established the presence of heroin in cases of acute narcotic intoxication. These studies demonstrated that measurement of heroin and its metabolites provides useful information for the differential diagnosis of heroin-related deaths.

To determine the degree of ethanol absorption and the resultant formation and urinary excretion of its conjugated metabolites following intensive use of high ethanol content mouthwash, 10 subjects gargled with Listerine(®) antiseptic 4 times daily for 3¼ days. First morning void urine specimens were collected on each of the four study days and post-gargle specimens were collected at 2, 4, and 6 h after the final gargle of the study. Urine ethanol, ethyl glucuronide (EtG), ethyl sulfate (EtS), and creatinine were measured. Ethanol was below the positive threshold of 20 mg/dL in all of the urine specimens. EtG was undetectable in all pre-study urine specimens, but two pre-study specimens had detectable EtS (6 and 82 ng/mL; 16 and 83 μg/g creatinine). Only one specimen contained detectable EtG (173 ng/mL; 117 μg/g creatinine). EtS was detected in the urine of seven study subjects, but was not detected in the single specimen that had detectable EtG. The maximum EtS concentrations were 104 ng/mL and 112 μg/g creatinine (in different subjects). Three subjects produced a total of eight (non-baseline) urinary EtS concentrations above 50 ng/mL or 50 μg/g creatinine and three EtS concentrations exceeding 100 ng/mL or 100 μg/g creatinine. In patients being monitored for ethanol use by urinary EtG and EtS concentrations, currently accepted EtG and EtS cutoffs of 500 ng/mL are adequate to distinguish between ethanol consumption and four times daily use of high ethanol content mouthwash.

To assess the degree of ethanol absorption and subsequent formation of urinary ethyl glucuronide (EtG) and ethyl sulfate (EtS) following sustained application of hand sanitizer, 11 volunteers cleansed their hands with Purell(™) hand sanitizer (62% ethanol) every 5 min for 10 h on three consecutive days. Urine specimens were obtained at the beginning and end of each day of the study, and on the morning of the fourth day. Urinary creatinine, ethanol, EtG, and EtS concentrations were measured. EtG was undetectable in all pre-study urine specimens, but two pre-study specimens had detectable EtS (73 and 37 ng/mL). None of the pre-study specimens had detectable ethanol. The maximum EtG and EtS concentrations over the course of the study were 2001 and 84 ng/mL, respectively, and nearly all EtG- and EtS-positive urine specimens were collected at the conclusion of the individual study days. Only two specimens had detectable EtG at the beginning of any study day (96 and 139 ng/mL), and only one specimen had detectable EtS at the beginning of a study day (64 ng/mL), in addition to the two with detectable EtS prior to the study. Creatinine-adjusted maximum EtG and EtS concentrations were 1998 and 94 μg/g creatinine, respectively. In patients being monitored for ethanol use by urinary EtG concentrations, currently accepted EtG cutoffs do not distinguish between ethanol consumption and incidental exposures, particularly when urine specimens are obtained shortly after sustained use of ethanolcontaining hand sanitizer. Our data suggest that EtS may be an important complementary biomarker in distinguishing ethanol consumption from dermal exposure.

The purity of illicit heroin in the United States has increased steadily over the last several years, while prices have fallen. Associated with this trend, there has been a recent shift among heroin addicts from intravenous injection to intranasal use ("snorting"). Because of the lack of information on this route of administration, we evaluated the pharmacokinetic and pharmacodynamic properties of intranasal heroin. Results were compared to the effects of heroin by the intramuscular route. Six healthy, male volunteers were administered single doses of intranasal heroin hydrochloride (6 and 12 mg), intramuscular heroin hydrochloride (6 mg), and placebo. Blood levels of heroin, 6-acetylmorphine, and morphine were measured by gas chromatography/mass spectrometry. Simultaneous physiological, behavioral, and performance measures were obtained. Peak blood levels of heroin were attained within 5 min of heroin administration by the intranasal route, similar to those observed for intramuscular administration. Generally, the pharmacokinetic profile of intranasal heroin was equivalent to that for the intramuscular route. Physiological, behavioral, and performance effects following intranasal administration were similar to the effects following intramuscular administration. The relative potency of intranasal heroin was estimated to be approximately one-half that of intramuscular administration. The efficacy of the intranasal route, combined with decreased heroin cost, reduced fear of infection, and the lack of requirements for additional drug paraphernalia, could make this an attractive route of drug administration to naive or infrequent drug users.

The realist prescription that Europe should fear the Germans is misguided. The modern Federal Republic deviates from the characteristics traditionally attributed to realist states. Instead of acting as a coherent unit set on maximising its power, the German state is defined by its strong regional governments and corporations and a power‐sharing central government. While German history calls for vigilance, there is good reason to believe that the Federal Republic's commitment to liberal democratic values will be lasting. The Germans face a daunting task in rebuilding the east, and other west Europeans should fear more their failure than their success.

A solid-phase extraction procedure was developed for the isolation of heroin, 6-acetylmorphine, and morphine from blood, plasma, saliva, and urine with subsequent assay by gas chromatography/mass spectrometry. Aprotic solvents, mild elution conditions, and an enzyme inhibitor were used to ensure maximum analyte stability. Samples were extracted and the extract was divided into two equal portions. One portion was assayed directly for heroin; detector response was linear over a concentration range of 1.0 to 250 micrograms/L. The second part of the extract was reacted with N-methyl-bis-trifluoroacetamide and assayed for the trifluoroacetyl derivatives of 6-acetylmorphine and morphine; detector response was linear over a concentration range of 1.0 to 500 micrograms/L. The limit of sensitivity was 1.0 microgram/L for each analyte. Hydrolysis of heroin to 6-acetylmorphine during extraction and analysis was < 5%. The method can be used to corroborate heroin use and to study the pharmacological effects of heroin and its metabolites.

The terms ‘false-positive’ and ‘false-negative’ are widely used in discussions of urine drug test (UDT) results. These terms are inadequate because they are used in different ways by physicians and laboratory professionals and they are too narrow to encompass the larger universe of potentially misleading, inappropriate and unexpected drug test results. This larger universe, while not solely comprised of technically ‘true’ or ‘false’ positive or negative test results, presents comparable interpretive challenges with corresponding clinical implications. In this review, we propose the terms ‘potentially inappropriate’ positive or negative test results in reference to UDT results that are ambiguous or unexpected and subject to misinterpretation. Causes of potentially inappropriate positive UDT results include in vivo metabolic conversions of a drug, exposure to nonillicit sources of a drug and laboratory error. Causes of potentially inappropriate negative UDT results include limited assay specificity, absence of drug in the urine, presence of drug in the urine, but below established assay cutoff, specimen manipulation and laboratory error. Clinical UDT interpretation is a complicated task requiring knowledge of recent prescription, over-the-counter and herbal drug administration, drug metabolism and analytical sensitivities and specificities.

Oxycodone is a semisynthetic opioid analgesic used in pain management. In the following method, gas chromatography-mass spectrometry (GC-MS) is used to determine the presence and concentration of the drug in blood and urine. The specimens are fortified with deuterated internal standard and a five-point calibration curve is constructed. Specimens are extracted using mixed-mode solid phase extraction and derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) producing trimethylsilyl derivatives. The final extracts are then analyzed using selected ion monitoring GC-MS.

The benzodiazepine assay utilizes gas chromatography-mass spectrometry (GC-MS) for the analysis of diazepam, nordiazepam, oxazepam, temazepam, lorazepam, alpha-hydroxyalprazolam, and alpha-hydroxytriazolam in blood and urine. A separate assay is employed for the analysis of alprazolam. Prior to solid phase extraction, urine specimens are subjected to enzyme hydrolysis. The specimens are fortified with deuterated internal standard and a five-point calibration curve is constructed. Specimens are extracted by mixed-mode solid phase extraction. The benzodiazepine extracts are derivatized with N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSFTA) producing tert-butyldimethyl silyl derivatives; the alprazolam extracts are reconstituted in methanol without derivatization. The final extracts are then analyzed using selected ion monitoring GC-MS.

Fentanyl is a potent, short-acting synthetic opioid analgesic. Fentanyl is measured in blood and urine following mixed-mode solid phase extraction. The specimens are fortified with deuterated internal standard and a five-point calibration curve is constructed. The final extracts are reconstituted in methanol and analyzed using selected ion monitoring gas chromatography-mass spectrometry.

Publisher Summary This chapter focuses on forensic toxicology, which is the study and practice of the application of toxicology for the purposes of the law. It demands the pursuit of scientific discovery within the rigors of the legal system to emphasize truth (accuracy), justice (impartiality), and the public good. Due to various technological and procedural advances, this field has matured into three distinct disciplines, which include postmortem forensic toxicology, human performance forensic toxicology, and forensic urine drug testing. Postmortem forensic toxicology determines the absence or presence of drugs and their metabolites, chemicals such as ethanol and other volatile substances, carbon monoxide and other gases, metals, and other toxic chemicals in human fluids and tissues, and evaluates their role as a determinant or contributory factor in the cause and manner of death. Human performance forensic toxicology, also known as behavioral toxicology, determines the absence or presence of ethanol and other drugs and chemicals in blood, breath, or other appropriate specimen(s), and evaluates their role in modifying human performance or behavior. Forensic urine drug testing determines the absence or presence of drugs and their metabolites in urine to demonstrate prior use or abuse. In forensic toxicology, each specimen is tracked by detailed documentation, from the time of its collection to the time of its disposal, and then each positive result is confirmed by a second analytical test before being reported.

A fatality due to the ingestion of bupropion and ethanol is presented. Bupropion and its metabolites were extracted from several tissues and identified using gas chromatography with nitrogenphosphorus and mass spectrometry detection. The concentrations of bupropion, hydroxybupropion and the erythroamino and threoamino alcohol metabolites in heart blood were 4.2, 5.0, 0.6 and 4.6 mg/l, respectively. The heart blood ethanol concentration was 0.27 g/dl. In addition, bupropion was distributed as follows: subclavian blood, 6.2 mg/l; bile, 1.4 mg/l; kidney, 2.4 mg/l; liver, 1.0 mg/kg; stomach contents, 16 mg and urine, 37 mg/l.

A case is presented where an individual ingested a fatal dose of chloral hydrate. Trichloroethanol (TCE), the metabolite of chloral hydrate, was initially identified by the Fujiwara reaction and quantified by gas chromatography/mass spectrometry in blood )127 mg/l), urine (128 mg/l) and stomach contents (25 mg total).

Forensic urine drug-testing laboratories routinely evaluate the suitability of urine specimens to assess potential adulteration, substitution, or dilution. For example, the measurement of urinary creatinine and specific gravity is performed by these laboratories to determine whether a specimen is abnormally dilute (1). Creatine is synthesized endogenously and is stored in skeletal muscle in a high-energy phosphorylated form. During muscle contraction, creatine and creatine phosphate are spontaneously converted to creatinine. Creatinine is eliminated from the body by renal excretion at a relatively constant rate, making it a clinically chosen measurement to indicate renal function and a forensically chosen measurement to detect dilute urine and potentially adulterated specimens (2). Creatine has been available since the early 1960s as a dietary supplement purported to ergogenically enhance short-term, high-intensity exercise (3)(4). However, it was not until the 1990s, when oral creatine supplements became widely available over the counter, that creatine became a popular …

Oxycodone is a semisynthetic opioid analgesic used in pain management. In the following method, gas chromatography-mass spectrometry (GC-MS) is used to determine the presence and concentration of the drug in blood and urine. The specimens are fortified with deuterated internal standard and a five-point calibration curve is constructed. Specimens are extracted using mixed-mode solid phase extraction and derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) producing trimethylsilyl derivatives. The final extracts are then analyzed using selected ion monitoring GC-MS.

The benzodiazepine assay utilizes gas chromatography-mass spectrometry (GC-MS) for the analysis of diazepam, nordiazepam, oxazepam, temazepam, lorazepam, alpha-hydroxyalprazolam, and alpha-hydroxytriazolam in blood and urine. A separate assay is employed for the analysis of alprazolam. Prior to solid phase extraction, urine specimens are subjected to enzyme hydrolysis. The specimens are fortified with deuterated internal standard and a five-point calibration curve is constructed. Specimens are extracted by mixed-mode solid phase extraction. The benzodiazepine extracts are derivatized with N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSFTA) producing tert-butyldimethyl silyl derivatives; the alprazolam extracts are reconstituted in methanol without derivatization. The final extracts are then analyzed using selected ion monitoring GC-MS.

Fentanyl is a potent, short-acting synthetic opioid analgesic. Fentanyl is measured in blood and urine following mixed-mode solid phase extraction. The specimens are fortified with deuterated internal standard and a five-point calibration curve is constructed. The final extracts are reconstituted in methanol and analyzed using selected ion monitoring gas chromatography-mass spectrometry.

The opioid and 6-acetylmorphine assays utilize gas chromatography-mass spectrometry (GC-MS) for the analysis of morphine, codeine, hydromorphone, hydrocodone, and 6-acetylmorphine in blood and urine. The specimens are fortified with deuterated internal standard and a five-point calibration curve is constructed. Specimens are extracted by mixed-mode solid phase extraction. The morphine, codeine, hydromorphone, hydrocodone, and 6-acetylmorphine extracts are derivatized with N-methyl-bis(trifluoroacetamide) (MBTFA) producing trifluoroacetyl derivatives. The final extracts are then analyzed using selected ion monitoring GC-MS.

Background: Many population studies find that alcohol prices are inversely related to alcohol consumption and alcohol-related problems, including among college students and young adults. Yet, little is known about the "micro-level" effects of alcohol price on the behavior of individual consumers in natural drinking settings such as college bars. Therefore, we assessed patron's cost per gram of ethanol consumed at on-premise drinking establishments and its association with intoxication upon leaving an establishment. Methods: On 4 consecutive nights during April 2008, data were collected from 804 patrons exiting 7 on-premise establishments in a bar district located adjacent to a large university campus in the southeastern United States. Anonymous interview and survey data were collected as well as breath alcohol concentration (BrAC) readings. We calculated each patron's expenditures per unit of ethanol consumed based on self-reported information regarding the type, size, number, and cost of consumed drinks. Results: A multivariable model revealed that a 10-cent increase in cost per gram of ethanol at on-premise establishments was associated with a 30% reduction in the risk of exiting an establishment intoxicated (i.e., BrAC >/= 0.08 g/210 l). Conclusions: The results are consistent with economic theory and population-level research regarding the price elasticity of alcoholic beverages, which show that increases in alcohol prices are accompanied by less alcohol consumption. These findings suggest that stricter regulation of the drink discounting practices of on-premise drinking establishments would be an effective strategy for reducing the intoxication levels of exiting patrons. Language: en

Hair samples from 20 documented heroin users contained 6-acetylmorphine, a unique metabolite of heroin, in all samples. Heroin was identified in smaller amounts in seven of these samples. The identity of 6-acetylmorphine and heroin was established by comparison of full scan spectra of extracts to standard reference materials. The presence of 6-acetylmorphine generally predominated over heroin, morphine, and codeine. The mean concentrations of analytes were as follows: 6-acetylmorphine, 0.90 ng/mg, N = 20; heroin, 0.17 ng/mg, N = 7; morphine, 0.26 ng/mg, N = 20; codeine, 0.18 ng/mg, N = 15. Analysis of hair samples obtained from 10 drug-free control subjects were negative for 6-acetylmorphine, morphine, and codeine. However, a small interfering peak was observed at the retention time for heroin. Control samples soaked in aqueous solutions of heroin and 6-acetylmorphine were found to be contaminated, even though an initial wash step was included in the analysis. These data suggest that hair analysis for 6-acetylmorphine can be used to differentiate heroin users from other types of opiate exposure (e.g., poppy seed, licit morphine, and codeine); however, environmental contamination can potentially produce false positives during opiate testing.

Comprehensive and rapid screening of specimens that enter a postmortem forensic toxicology laboratory is essential. Although blood and urine specimens are most commonly utilized for immunoassay screening, this study illustrates the use of vitreous humor for similar purpose. Over a 2-year period, 1233 out of 5471 cases submitted for drug analysis were screened for the presence of opioids in vitreous humor by the Microgenics Cloned Enzyme Donor Immunoassay (CEDIA) DAU opiate assay. Eighty-five of these cases were presumptively opioid positive by the opiate assay. In 75 of the 85 cases (88.2%), at least one opioid | was subsequently confirmed in blood and/or bile. The gas chromatography-nitrogen-phosphorus detection (GC-NPD) screening method employed by this laboratory detected the presence of opioids in 20 of the 75 opioid-confirmed cases (26.6%). Codeine and oxycodone were readily identified by the GC-NPD screen; however, morphine, hydrocodone, hydromorphone, and 6-acetylmorphine were detected primarily by gas chromatography-mass spectrometry. In summary, the CEDIA DAU opiate assay improved the detection of opioids in our casework for the period studied by 1.0% (55/5471).