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An important role of modern forensic and clinical toxicologists is to monitor the adverse events of novel psychoactive substances (NPS). Following a prior review from 2013 to 2016, this critical literature review analyzes and evaluates published case reports for NPS from January 2017 through December 2020. The primary objective of this study is to assist in the assessment and interpretation of these cases as well as provide references for confirmation methods. Chemistry, pharmacology, adverse events and user profiles (e.g., polypharmacy) for NPS are provided including case history, clinical symptoms, autopsy findings and analytical results. Literature reviews were performed in PubMed and Google Scholar for publications using search terms such as NPS specific names, general terms (e.g., ‘designer drugs’ and ‘novel psychoactive substances’), drug classes (e.g., ‘designer stimulants’) and outcome-based terms (e.g., ‘overdose’ and ‘death’). Government and website drug surveillance databases and abstracts published by professional forensic science organizations were also searched. Toxicological data and detailed case information were extracted, tabulated, analyzed and organized by drug category. Case reports included overdose fatalities (378 cases), clinical treatment and hospitalization (771 cases) and driving under the influence of drugs (170 cases) for a total of 1,319 cases providing details of adverse events associated with NPS. Confirmed adverse events with associated toxidromes of more than 60 NPS were reported including synthetic cannabinoid, NPS stimulant, NPS hallucinogen, NPS benzodiazepine and NPS opioid cases. Fifty of these NPS were reported for the first time in January 2017 through December 2020 as compared to the previous 4 years surveyed. This study provides insight and context of case findings described in the literature and in digital government surveillance databases and websites during a recent 4-year period. This review will increase the awareness of adverse events associated with NPS use to better characterize international emerging drug threats.

In 2007, the Bureau of Justice Statistics reported on 2004 data collected from the Census of Medical Examiner and Coroner Offices (CMEC). The CMEC was one of the first comprehensive reports on the state of the medicolegal death investigation system in the United States and included information on administration, expenditure, workload, specialized death investigations, records and evidence retention, and resources. However, the report did not include responses on questions that were related to toxicology such as specimen retention and type of testing. The purpose of this publication is to provide the community with toxicology laboratory‐specific responses from nearly 2000 medical examiner and coroner (MEC) offices. Data obtained from a BJS CMEC public use dataset for any remaining information that was not reported in the 2007 BJS report were evaluated specific to the operation of toxicology laboratories within a MEC office or specific to toxicology testing. The CMEC includes information on average operating budget for MEC offices with internal or external toxicology services, budget for toxicology/microbiology services, respondents’ routine uses of toxicology analysis, toxicology specimen retention time, average turnaround times, use of computerized information management systems, and participation in federal data collections. These historical data begin to address the present state of our nation’s toxicology laboratories within the medicolegal death investigation system and their preparedness for the current drug overdose epidemic.

In 2009, the Palm Beach County Sheriff’s Office Forensic Biology Unit developed an innovative DNA backlog strategy to construct and operate a centralized biological processing laboratory (BPL) within a law enforcement agency, the Boca Raton Police Services Department. The BPL became fully operational in 2012 and obtained accreditation in 2017. This coordinated, multi-agency agreement resulted in a streamlined process exemplifying several benefits such as communicating timely testing results, decreasing the case turnaround time, and decreasing the DNA case backlog. This paper provides a summary of the necessary considerations of location, construction, personnel, and services when constructing a BPL, as well as, provides a comparison of initial completion dates and ultimate completion dates over a three-year period from 2016 to 2018. Three LEAs submitted 613 cases to the BPL commensurate with jurisdictional population. Performance metrics such as types and number of criminal cases screened; the number of samples forwarded for PBSO DNA testing; the turnaround time to handle, screen, or analyze a forensic sample; evidentiary samples; and the number of profiles entered into the Combined DNA Index System (CODIS) database are reported. For example, prior to this DNA backlog reduction strategy, the FBU was taking an average of 153 days to handle, screen, or analyze a forensic sample from submission to final report and there was a backlog of 679 cases. From 2016 to 2018, the total average turnaround time for BPL decreased from 30.5 to 19.6 days, (35.8% decrease); and the FBU Request turnaround time decreased from 153 to 80 days (35% decrease). Monitoring laboratory metrics demonstrate the efficacy of the DNA backlog reduction strategy. There are several takeaway lessons from this experience, including (1) engaging legal counsel early to outline necessary legal procedures and the timeline; (2) bringing all stakeholders “to the table” early to discuss expectations, as well as legal and operational responsibilities; and (3) creating a realistic timeline as well as establishing a comprehensive memorandum of understanding by which all parties understand their roles and responsibilities. Understanding laboratory and non-laboratory policy issues is critical to implementation success and the efficacy of a BPL as a DNA backlog reduction strategy.

The November 2017 release of the Council of Economic Advisers’ White House report on the opioid crisis suggests that prior consideration of expenses severely underestimated the economic costs of the opioid crisis. When corrected for these losses, the annual cost from the opioid crisis leapt nearly 600%. The cost to the criminal justice system was estimated at $8 Billion of which $270 million is borne by crime laboratories. However, laboratory budgets have not grown at a rate capable of meeting this increased demand for forensic science services. The hidden costs of the opioid crisis borne by the forensic crime laboratories comes as funds are diverted in the laboratory to meet the increased demands for services in drug chemistry and toxicology. Dramatic increases in turnaround times across other areas of investigation continue to grow as the crisis accelerates. Keywords: Opioid crisis, Toxicology, Policy, Crime laboratories

The National Institute of Justice (NIJ) and its Forensic Technology Center of Excellence (FTCoE) hosted the National Opioid and Emerging Drug Threats Policy and Practice Forum on July 18–19, 2019, in Washington, DC. The forum explored ways in which government agencies and programs, law enforcement officials, forensic laboratory personnel, medical examiners and coroners, researchers, and other experts can cooperate to respond to problems associated with drug abuse and misuse. Panelists from these stakeholder groups discussed ways to address concerns such as rapidly expanding crime laboratory caseloads; workforce shortages and resiliency programs; analytical challenges associated with fentanyl analogs and drug mixtures; laboratory quality control; surveillance systems to inform response; and policy related to stakeholder, research, and resource constraints. The NIJ Policy and Practice Forum built off the momentum of previous stakeholder meetings convened by NIJ and other agencies to discuss the consequences of this national epidemic, including the impact it has had on public safety, public health, and the criminal justice response. The forum discussed topics at a policy level and addressed best practices used across the forensic community.

In many jurisdictions, public safety and public health entities are working together to enhance the timeliness and accuracy of the analytical characterization and toxicology testing of novel synthetic opioids. The improved sharing and early detection of these analytical data are intended to inform surveillance, interdiction efforts, patient intervention and treatment, all of which are critical to curbing the opioid epidemic. Forensic practitioners working to identify novel synthetic opioids struggle to provide timely results when encountering new or unknown substances, such as the fentanyl analogs. These compounds, which mimic heroin in pharmacologic effect but can be far more potent, are inconsistently present in chemical identification libraries, and are currently largely unavailable as reference materials for analytical comparison. Additionally, federal, state and local governments as well as nongovernmental organizations require potency, toxicity and potential-for-abuse data to evaluate the potential health risks of emerging drug threats. Subsequent scheduling efforts and criminal prosecutions also require these thorough drug characterization studies. Pilot programs have demonstrated that early communication of real-time drug toxicity and analytical data significantly impacts the successful response to emerging opioids. High-quality, real-time, national-level data on chemical composition, toxicological test data, drug toxicity and overdoses, and analysis of seized materials by law enforcement are needed to track drug trends. However, the USA still lacks a national system to coordinate and communicate toxicology, medical and medical examiner and coroner data with the broader medical and law enforcement communities. Opportunities to address these gaps as well as recent advancements collected through interagency efforts and technical workshops in the toxicology and analytical chemistry communities are presented here. Opportunities for partnership, increased communication and expanding best practices to move toward an integrated, holistic analytical response are also explored.

On May 10–11, 2016, the US Department of Justice (DOJ) National Institute of Justice (NIJ), the Netherlands Forensic Institute (NFI; Dutch Ministry of Security and Justice of the Netherlands), the International Society for Forensic Radiology and Imaging (ISFRI), the International Association of Forensic Radiographers (IAFR), and NIJ’s Forensic Technology Center of Excellence (FTCoE) at RTI International organized and convened the International Forensic Radiology Research Summit (IFRRS) at the Academic Medical Center in Amsterdam. The summit assembled 40 international subject matter experts in forensic radiology, to include researchers, practitioners, government employees, and professional staff from 14 countries. The goal of this 2-day summit was to identify gaps, challenges, and research needs to produce a road map to success regarding the state of forensic radiology, including formulating a plan to address the obstacles to implementation of advanced imaging technologies in medicolegal investigations. These proceedings summarize the meeting’s important exchange of technical and operational information, ideas, and solutions for the community and other stakeholders of forensic radiology.

This study is a 6-month retrospective analysis of urine drug testing (UDT) data from a pain management population among specimens with clinician-ordered marijuana testing (N = 194 809). Descriptive statistics about the specimen positivity of clinician-ordered marijuana UDT are provided as well as other drug positivity. Specimens from men and adults aged 18 to 34 years had the highest prevalence rates of marijuana positivity. The prevalence of past-month marijuana use among a comparative national population was lower than the prevalence of positive marijuana tests in the UDT specimens by all characteristics. Among the specimens tested for illicit drugs and marijuana, 4.0% were positive for amphetamine, 2.8% were positive for cocaine, and 0.9% were positive for heroin. The most common prescription drugs listed were opioids (64.7%), benzodiazepines (20.5%), and antidepressants (19.9%). In sum, the findings reflect previous research showing high rates of marijuana use, illicit drug use, and prescription drug use in a pain management population.

The Forensic Resource/Reference on Genetics-knowledge base (FROG-kb) web sitehttps://frog.med.yale.edu/FrogKB/was introduced in 2011 and in the five years since the previous publication ongoing research into how the database can better serve forensics has resulted in extensive redesign of the database interface and functionality. Originally designed as a prototype to support forensic use of single nucleotide polymorphisms (SNPs), FROG-kb provides a freely accessible web interface that facilitates forensic practice and can be useful for teaching and research. Based on knowledge gained through its use, the web interface has been redesigned for easier navigation through the multiple components. The site also has functional enhancements, extensive new documentation, and new reference panels of SNPs with new curated data. FROG-kb focuses on single nucleotide polymorphisms (SNPs) and provides reference population data for several published panels of individual identification SNPs (IISNPs) and several published panels of ancestry inference SNPs (AISNPs). For each of the various marker panels with reference population data, FROG-kb calculates random match probabilities (RMP) and relative likelihoods of ancestry for a user-entered genotype profile (either completely or partially specified). Example genotype profiles are available and the User's Manual presents interpretation guidelines for the calculations. The extensive documentation along with ongoing updates makes FROG-kb a comprehensive tool in facilitating use of SNPs in forensic practice and education. An overview of the new FROG-kb with examples and material explaining the results of its use are presented here.

Novel psychoactive substances (NPS) represent significant analytical and interpretive challenges to forensic and clinical toxicologists. Timely access to case reports and reports of adverse incidents of impairment or toxicity is imperative to clinical diagnosis and treatment, as well as to interpretation of forensic results. Delays in identifying the presence of a novel intoxicating agent have significant consequences for public health and public safety. Adverse effects of intoxications with novel cannabinoids, stimulants, hallucinogens, benzodiazepines and opioids spanning January 2013 through December 2016 as reported in emergency departments, death investigations, impaired driving cases and other forensic contexts are the subject of this review. Discussion of the chemistry, pharmacology and adverse events associated with novel drug classes is summarized and described within. Adverse effects or symptoms associated with ingestion of more than 45 NPS have been abstracted and summarized in tables, including demographics, case history, clinical or behavioral symptoms, autopsy findings and drug confirmations with quantitative results when provided. Based on these findings and gaps in the available data, we provide recommendations for future toxicological testing of these evolving substances. These include development and management of a national monitoring program to provide real-time clinical and toxicological data, confirmed analytically, on emerging drugs and their known toxidromes and side effect profiles. Increased efforts should be made to analytically confirm the agents responsible for clinical intoxications involving adverse events in emergency department admissions or hospitalizations. Evidence-based community preparedness among analytical laboratories gained through active communication and sharing of toxicological findings and trends in NPS is imperative to assist in enabling early detection of new drugs in forensic and clinical populations.

Hair specimens were analyzed for cocaine (COC), benzoylecgonine (BE), cocaethylene (CE) and norcocaine (NCOC) by liquid chromatography-tandem mass spectrometry. Drug-free hair was contaminated in vitro with COC from different sources with varied COC analyte concentrations. Results were compared to COC analyte concentrations in drug users' hair following self-reported COC use (Street) and in hair from participants in controlled COC administration studies (Clinical) on a closed clinical research unit. Mean ± standard error analyte concentrations in Street drug users' hair were COC 27,889 ± 7,846 (n = 38); BE 8,132 ± 2,523 (n = 38); CE 901 ± 320 (n = 20); NCOC 345 ± 72 pg/mg (n = 32). Mean percentages to COC concentration were BE 29%, CE 3% and NCOC 1%. Concentrations in hair were lower for Clinical participants. COC contamination with higher CE, BE or NCOC content produced significantly higher concentrations (P = 0.0001) of all analytes. CE/COC and NCOC/COC ratios did not improve differentiation of COC use from COC contamination. COC concentrations in illicit and pharmaceutical COC affect concentrations in contaminated hair. Criteria for distinguishing COC use from contamination under realistic concentrations were not significantly improved by adding CE and NCOC criteria to COC cutoff concentration and BE/COC ratio criteria. Current criteria for COC hair testing in many forensic drug-testing laboratories may not effectively discriminate between COC use and environmental COC exposure.

The use of forensic evidence in the criminal justice system has grown appreciably in the United States. Yet policies that dictate how state and local agencies maintain and store forensic evidence have not kept pace. This study examined the prevalence of evidence retention policies, as well as storage locations and tracking systems, in a nationally representative sample of state and local law enforcement agencies. Less than half of U.S. police departments have a policy for preserving biological evidence from convicted offenders. Among agencies having a policy, the responsibility for retaining evidence was most commonly placed with the investigating law enforcement agency. Implications of these findings and policy directions are discussed.

The crime laboratory has not typically been thought of as a decision stage within the criminal justice process. However, increasing reliance on forensic evidence has led to necessary discretion about what types of cases to accept, what evidence to analyze, and how to prioritize workload. This article reports the results of semi-structured interviews conducted with state and local police agencies, prosecutors, and crime laboratory personnel in ten U.S. jurisdictions. The focus is on controlled substances cases, which represent a substantial proportion of the case workload for crime laboratories, as well as for the police and prosecutors. Results demonstrate that communication between crime laboratories, the police, and prosecutors is essential to maximizing the efficient use of limited laboratory resources. Poor communication can contribute to overflowing police evidence rooms, confusion about evidence retention policies, rushed and unnecessary laboratory requests, and the generation of “artificia...

On November 25, 2008, the U.S. Department of Health and Human Services posted a final notice in the Federal Register authorizing the use of liquid chromatography-tandem mass spectrometry (LC-MS-MS) and other technologies in federally regulated workplace drug testing (WPDT) programs. These rules are expected to become effective in May 2010. To support this change, it is essential to explicitly demonstrate that LC-MS-MS as a technology can produce results at least as valid as gas chromatography-mass spectrometry (GC-MS), the long-accepted standard in confirmatory analytical technologies for drugs of abuse and currently the only confirmatory method allowed for use in support of federally regulated WPDT programs. A series of manufactured control urine samples (n = 10 for each analyte) containing benzoylecgonine, morphine, codeine, and 6-acetylmorphine at concentrations ranging from 10% to 2000% of federal cutoffs were analyzed with replication by five federally regulated laboratories using GC-MS (five replicate analyses per lab) and at RTI International using LC-MS-MS (10 replicate analyses). Interference samples as described in the National Laboratory Certification Program 2009 Manual were also analyzed by both GC-MS and LC-MS-MS. In addition, matrix effects were assessed for LC-MS-MS, and both analytical technologies were used to analyze previously confirmed urine specimens of WPDT origin. Results indicated that LC-MS-MS analysis produced results at least as precise, accurate, and specific as GC-MS for the analytes investigated in this study. Matrix effects, while evident, could be controlled by the use of matrix-matched controls and calibrators with deuterated internal standards. LC-MS-MS data parameters, such as retention time and product ion ratios, were highly reproducible.

Morphological changes in hair subjected to decontamination protocols were evaluated by scanning electron microscopy (SEM) as part of the National Laboratory Certification Program's (NLCP) efforts to develop proficiency testing materials in support of Federal Workplace Drug Testing programs. Hair from five different donors was evaluated. Hair samples were subjected to three decontamination protocols: (1) aqueous phosphate buffer, (2) methanol or (3) methylene chloride as models for aqueous, alcohol and polar organic solvent protocols, respectively. Under these protocols, samples of hair were treated for 225 min (aqueous), 15 min (alcohol), or 15 min (polar organic). After decontamination, hair strands were sputter coated with gold/palladium (AuPd) and observed by SEM. Modest lifting of cuticle scales was observed in hair treated with methanol and methylene chloride consistent with some changes to the cell membrane complex (CMC) between cuticle scales. Damage resulting from aqueous buffer treatment ranged from substantial degradation to apparent complete loss of cuticle scales. Fracture structures consistent with cuticle damage were also observed. Each decontamination protocol had a different impact on the cuticle of the hair shaft.

Atomoxetine (Strattera, Lilly) is a selective norepinephrine reuptake inhibitor (SNRI) prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. It is the first nonstimulant drug-therapy option for ADHD. Three case reports are presented in which atomoxetine was detected in two individuals who died from causes unrelated to the drug and a third from the intentional ingestion of atomoxetine and other drugs. In addition, a brief description of the pharmacokinetics and side effects of atomoxetine are given. Postmortem fluid and tissue concentrations of atomoxetine were as follows: aortic blood

Seven opioid analytes including codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, oxycodone, and oxymorphone were detected in postmortem blood (n > 1000). Two milliliters of specimen was deproteinated with approximately 2.5 mL of methanol and derivatized with hydroxylamine before solid-phase extraction and derivatization with BSTFA + 1% TMCS. Extracts were assayed by gas chromatography-electron impact-mass spectrometry utilizing selected ion mode. One-microliter aliquots were injected onto an HP-1MS capillary column (30 m x 0.25-mm i.d., 0.25 microm) with a helium linear velocity of 62 cm/s. Temperature programming began at 160 degrees C (hold 0 min), then increased at rates of 35 degrees C/min to 195 degrees C, 5 degrees C/min to 240 degrees C, and 30 degrees C/min to 300 degrees C (hold 2 min) resulting in a total run time of 14-min. Quantitative determinations were based on the ratios of the analyte peak areas to the corresponding deuterated analogues. Calibration curves were linear for the following concentrations: 10-500 ng/mL (6-AM), 100-2000 ng/mL (oxycodone), and 50-1000 ng/mL (all other opioids). LOQs ranged from 5 ng/mL (6-AM) to 20 ng/mL (oxycodone). Between-run precision yielded CVs ranging from 2.79% to 5.34% (n = 12). These data suggest that methanolic deproteination and dual derivatization improve separation and simultaneous quantitation of seven opioid analytes in difficult matrices.

CE update [generalist] New Insights into an Old Poison, Arsenic Catherine A. Hammett-Stabler, PhD, DABCC, FACB,1 Larry A. Broussard, PhD, DABCC, FACB,2 Ruth E. Winecker, PhD,3,1 Jeri D. Ropero-Miller, PhD3,1 1Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 2LSU Health Sciences Center, Clinical Laboratory Sciences, New Orleans, LA, 3Office of the Chief Medical Examiner, State of North Carolina, Chapel Hill, NC

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.

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.

On November 25, 2008, the U.S. Department of Health and Human Services posted a final notice in the Federal Register authorizing the use of liquid chromatography-tandem mass spectrometry (LC-MS-MS) and other technologies in federally regulated workplace drug testing (WPDT) programs. To support this change, it is essential to explicitly demonstrate that LC-MS-MS, as a technology, can produce results at least as valid as gas chromatography (GC)-MS, the long-accepted standard in confirmatory analytical technologies for drugs of abuse. A series of manufactured control urine samples (n = 10 for each analyte) containing amphetamine, methamphetamine, (±)-3,4-methylenedioxyamphetamine, (±)-3,4-methylenedioxymethamphetamine, (±)-3,4-methylenedioxyethylamphetamine, phencyclidine, and (±)-11-nor-9-carboxy-Δ 9 -tetrahydrocannabinol at concentrations ranging from 10% to 2000% of federal cutoffs were analyzed with replication by five federally regulated laboratories using GC-MS and at RTI International using LC-MS-MS. Interference samples as described in the National Laboratory Certification Program 2009 Manual were analyzed by GC-MS and LC-MS-MS as well as previously confirmed urine specimens of WPDT origin. Matrix effects were assessed for LC-MS-MS. Results indicated that LC-MS-MS analysis produced results at least as precise, accurate, and specific as GC-MS for the analytes investigated in this study. Matrix effects, while evident, could be controlled by the use of matrix-matched controls and calibrators with deuterated internal standards.

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 …

The National Laboratory Certification Program undertook an evaluation of the dynamics of external contamination of hair with cocaine (COC) while developing performance testing materials for Federal Drug-Free Workplace Programs. This characterization was necessary to develop performance materials that could evaluate the efficacy of hair testing industry's decontamination procedures. Hair locks (blonde to dark brown/black) from five different individuals were contaminated with cocaine HCl. Hair locks were then treated with a synthetic sweat solution and hygienic treatments to model real-life conditions. Hair locks were shampooed daily (Monday through Friday) for 10 weeks, and samples of the hair locks were analyzed for COC, benzoylecgonine (BE), cocaethylene (CE), and norcocaine (NCOC). Three commercial analytical laboratories analyzed samples under three protocols: no decontamination procedure, individual laboratory decontamination, or decontamination by an extended buffer procedure at RTI International. Results indicated substantial and persistent association of all four compounds with all hair types. Hair that was not decontaminated had significantly greater quantities of COC and BE than did hair that was decontaminated. The only hair samples below detection limits for all four compounds were those decontaminated 1 h after contamination. Additionally, BE/COC ratios increased significantly over the 10-week study (regardless of decontamination treatment). From 21 days postcontamination until the end of the study, the mean BE/COC ratio for all hair types exceeded 0.05, the proposed Federal Mandatory Guidelines requirement. The largest variability in results was observed for samples decontaminated by participant laboratories. This suggests that current laboratory decontamination strategies will increase variability of performance testing sample results. None of the decontamination strategies used in the study were effective at removing all contamination, and some of the contaminated hair in this study would have been reported as positive for cocaine use based on the proposed Federal Mandatory Guidelines.

The case history and toxicological findings of a fatal multi-drug overdose involving metaxalone (Skelaxin) are presented. Gas-liquid chromatography with flame-ionization detection and gas chromatography-mass spectrometry were used to determine the following drug concentrations (mg/L) in aortic blood: 19 mg/L metaxalone; 190 mg/L acetaminophen; 0.28 mg/L hydrocodone; and < 0.1 mg/L diazepam, nordiazepam, amitriptyline, and nortriptyline. The following concentrations of metaxalone were reported in alternate specimens: 17 mg/L in femoral blood; 44 mg/L in bile; 70 mg/kg in liver; 7 mg/L in urine; 202 mg/kg in gastric contents; and 14 mg/L in vitreous humor. These concentrations were determined using both direct extraction and the method of standard addition. The quantitative results obtained by both procedures were in good agreement. Because of the limited information published on metaxalone toxicity, the pathologist assigned the manner and cause of death as accidental acute hydrocodone intoxication. Four additional cases in which metaxalone was present were analyzed for comparison. Two cases were probable drug-related deaths and had metaxalone aorta blood concentrations of 18 and 11 mg/L. The other two cases had therapeutic metaxalone concentrations in the aortic blood of < 0.75 and 2.1 mg/L.

Estimates suggest that more than 5A million U.S. citizens unknowingly have diabetes and are at increased risk of morbidity and mortality. We evaluated an immunoturbidimetric measurement of glycated hemoglobin (%HbA1c) as a postmortem tool to identify such individuals. Although postmortem samples undergo some degradation, the effects are not sufficient to invalidate the use of the test or method. Using two study populations whose medical history of diabetes was known, we found the mean %HbA1c of the non-diabetics (5.8+/-0.3) to be statistically different from that of the diabetics (12.4+/-2.8). For the population whose disease status was unknown, the %HbA1c ranged from 4.7 to 16.8. For six unknowns whose values exceeded 7.0%. the mean was 11.7%, which did not differ statistically from the diabetic mean (p = 0.6615). These studies suggest that postmortem blood samples can be used to characterize HbA1c values.

© One major class of designer drugs is the amphetamine analogs. Ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] is an amphetamine analog. Amphetamine analogs are categorized as “designer drugs” because “street” chemists design and synthesize them to mimic the central nervous system (CNS) and hallucinogenic effects of other illicit (controlled) drugs. Changes to the chemical structure allow the newly synthesized drugs to escape regulation until the legal authorities discover their existence. Once recognized as having no medicinal purpose and a high potential for abuse, amphetamine analogs are primarily scheduled as Class I drugs in most countries. Ecstasy is taken orally in doses from 100 to 150 mg. The first patent for MDMA was in 1914 as an appetite suppressant for soldiers in World War I. Additional therapeutic purposes include psychotherapy aid, treatment of terminal cancer patients to relieve pain and emotional stress, and treatment of patients suffering from post-traumatic stress disorder, anxiety, depression, and schizophrenia. Ecstasy is abused for its psychoactive and hallucinogenic effects, the latter being less intense than LSD or mescaline. According to the 2001 National Household Survey on Drug Abuse, an estimated 8.1 million (3.6%) Americans age 12 or older tried MDMA at least once in their lifetimes, up from 6.5 million (2.9%) in 2000. Desired effects of MDMA are summarized in T1. Known as an entactogen, MDMA promotes enhanced sociability, affability, and a feeling of closeness. As illustrated by magnetic resonance imaging, MDMA causes longterm damage to serotonin-containing neurons in the brain, which can adversely affect emotions, memory, sleep, pain, and higher order cognitive processes.

Benzodiazepines are used therapeutically as antidepressant, anxiolytic, anticonvulsant, hypnotic, muscle relaxant, and preanesthetic agents. Moreover, benzodiazepines are often abused for their euphoric effects. Consequently, benzodiazepines are commonly detected in toxicological analyses. Immunoassays of benzodiazepines are plagued by several factors that make reliable detection difficult. Complicated metabolic pathways, including N -dealkylation, C -hydroxylation, and glucuronidation, effectively reduce the parent compound to more polar, and thus easily excreted, metabolites. Some of these metabolites are pharmacologically active; in some cases, they are present in higher concentrations and have a longer elimination half-life than the parent compound (1)(2). Many, especially the glucuronide conjugates, which appear at high concentrations in the urine, do not readily cross-react with commercial immunoassays. In contrast, other benzodiazepine metabolites demonstrate high cross-reactivity, depending on the immunoassay utilized (3). In the US, 13 benzodiazepines of various potencies are commonly prescribed. Therapeutic daily doses have substantially decreased with the newer generation of benzodiazepines (2). Variations in dosage and in ultimate excretion patterns complicate the ability to accurately detect benzodiazepine use (4). Accumulated research findings indicate pretreating urine specimens with β-glucuronidase (EC 3.2.1.31) increases the diagnostic …

Estimates suggest that more than 5.4 million U.S. citizens unknowingly have diabetes and are at increased risk of morbidity and mortality. We evaluated an immunoturbidimetric measurement of glycated hemoglobin (%HbA1c) as a postmortem tool to identify such individuals. Although postmortem samples undergo some degradation, the effects are not sufficient to invalidate the use of the test or method. Using two study populations whose medical history of diabetes was known, we found the mean %HbA1c of the non-diabetics (5.8 ± 0.3) to be statistically different from that of the diabetics (12.4 ± 2.8). For the population whose disease status was unknown, the %HbA1c ranged from 4.7 to 16.8. For six unknowns whose values exceeded 7.0%, the mean was 11.7%, which did not differ statistically from the diabetic mean (p = 0.6615). These studies suggest that postmortem blood samples can be used to characterize HbA1c values.

Fingernail and toenail specimens were obtained from 18 suspected cocaine users. The nails were cut, heated under methanolic reflux, and the methanolic extracts were purified by solidphase extraction. Gas chromatography/mass spectrometry was utilized for the qualitative and quantitative analysis of nine cocaine analytes. Comparison of conventional postmortem analysis of blood and urine with nail analysis revealed a marked increase in the detection of cocaine use by nail analysis. Cocaine analytes were present in 14 (82.3%) subjects utilizing nail analysis. Out of those 14 subjects, only 5 (27.7%) were positive by conventional postmortem drug analysis. Cocaine and benzoylecgonine were the predominant analytes in all positive nail specimens. Anhydroecgonine methyl ester, ecgonine methyl ester, ecgonine ethyl ester, cocaethylene, norcocaine, and norbenzoylecgonine were detected in a limited number of specimens. The ratio of cocaine to benzoylecgonine ranged from 2–10:1. These findings suggest that nails may be a useful alternative matrix for the detection of cocaine exposure.