Tolerant or Intolerant? Learning From Studying Drug Concentrations in the Living and the Dead.

Tolerance is the diminished response to a drug that occurs when that drug is repeatedly used, and the body adapts to its continued presence. This means that greater blood concentrations are required to achieve desired effects, produce impairment, or cause death. Without case-specific information, the pharmacodynamic impacts of a drug on an individual are difficult to ascertain based on its concentration alone.

Xylazine: Pharmacology Review and Prevalence and Drug Combinations in Forensic Toxicology Casework.

Xylazine, an alpha-2 receptor agonist used in veterinary medicine for its sedative and muscle-relaxant effects, has been reported in forensic toxicology casework since the 1980s. It is not approved for human use, but it is used as an adulterant in heroin and illicit fentanyl. The prevalence and concentrations of xylazine in 2.

Reports of Adverse Events Associated with Use of Novel Psychoactive Substances, 2017-2020: A Review.

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.

Brorphine-Investigation and quantitation of a new potent synthetic opioid in forensic toxicology casework using liquid chromatography-mass spectrometry.

New synthetic opioids continue to appear as novel psychoactive substances (NPS) on illicit drug markets. Isotonitazene emerged in mid-2019, becoming the most prevalent NPS opioid in the United States within a few months. Notification by the Drug Enforcement Administration of its intent to schedule isotonitazene in mid-2020 led to its decline in popularity and replacement with a new NPS opioid: brorphine.

Isotonitazene Quantitation and Metabolite Discovery in Authentic Forensic Casework.

The synthetic opioid landscape continues to change as non-fentanyl-related substances appear in forensic toxicology casework. Among the newest synthetic opioids to emerge is isotonitazene, an analogue of a benzimidazole class of analgesic compounds. Isotonitazene is an active and potent synthetic opioid, but the extent to which this compound is causing toxicity among drug users was previously unknown.

4F-MDMB-BINACA: A New Synthetic Cannabinoid Widely Implicated in Forensic Casework.

This is the first report regarding the characterization of the new synthetic cannabinoid 4F-MDMB-BINACA. 4F-MDMB-BINACA was first analytically confirmed in seized drug material using gas chromatography-mass spectrometry (GC-MS), liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF), and nuclear magnetic resonance (NMR) spectroscopy. Subsequent to this characterization, 4F-MDMB-BINACA was detected in biological specimens collected as part of forensically relevant casework, including medicolegal death investigations and drug impaired driving investigations, from a variety of regions in the United States.

Quantification of Designer Opioids by Liquid Chromatography-Tandem Mass Spectrometry.

Opioids including heroin and commonly prescribed drugs such as oxycodone and fentanyl are among the most commonly abused drugs. In recent years, the abuse of opioids has spread beyond these commonly encountered analytes and now includes novel psychoactive drugs such as AH-7921 and U47700 and a variety of fentanyl-related compounds such as acetyl fentanyl and furanyl fentanyl. The assay described is for the quantitative determination of 19 designer opioids in serum, plasma, and whole blood.

The Evolving Landscape of Designer Drugs.

Since 2008 there has been an onslaught of new drugs in the illicit marketplace. Often referred to as "research chemicals," "designer drugs," or "novel psychoactive substances" (NPS), these substances are used for their pharmacological effects which are often similar to more widely known drugs such as ecstasy or heroin. In some cases users specifically seek out these new chemicals, in other cases they are simply purchasing what they believe to be their normal drug of choice from a dealer, but the product is not what it is purported to be.

Reports of Adverse Events Associated with Use of Novel Psychoactive Substances, 2013-2016: A Review.

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.

Analysis of Novel Synthetic Opioids U-47700, U-50488 and Furanyl Fentanyl by LC-MS/MS in Postmortem Casework.

Following series of synthetic cannabinoid and synthetic cathinone derivatives, the illicit drug market has begun to see increased incidence of synthetic opioids including fentanyl and its derivatives, and other chemically unrelated opioid agonists including AH-7921 and MT-45. Among the most frequently encountered compounds in postmortem casework have been furanyl fentanyl (N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylfuran-2-carboxamide, Fu-F) and U-47700 (trans-3,4-dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide). Both drugs have been reported to be present in the heroin supply and to be gaining popularity among recreational opioid users, but were initially developed by pharmaceutical companies in the 1970s as candidates for development as potential analgesic therapeutic agents.

Development and validation of a liquid chromatography-tandem mass spectrometry method for the identification and quantification of JWH-018, JWH-073, JWH-019, and JWH-250 in human whole blood.

A sensitive and specific method for the quantification of JWH-018, JWH-073, and JWH-250 and the qualitative identification of JWH-019 in whole blood was developed and validated. Samples fortified with JWH-018-d₉ and JWH-073-d₉ underwent liquid-liquid extraction and were analyzed by liquid chromatography-positive ion electrospray ionization-tandem mass spectrometry. Two transitions were monitored for all analytes except JWH-250, for which there was only one available transition.

Urinary excretion of buprenorphine, norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine-glucuronide in pregnant women receiving buprenorphine maintenance treatment.

Background: Buprenorphine (BUP) is under investigation as a medication therapy for opioid-dependent pregnant women. We investigated BUP and metabolite disposition in urine from women maintained on BUP during the second and third trimesters of pregnancy and postpartum.

Methods: We measured BUP, norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and NBUP-Gluc concentrations in 515 urine specimens collected thrice weekly from 9 women during pregnancy and postpartum.

Development and validation of a liquid chromatography-tandem mass spectrometry assay for the simultaneous quantification of buprenorphine, norbuprenorphine, and metabolites in human urine.

A liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and norbuprenorphine glucuronide (NBUP-Gluc) in human urine was developed and fully validated. Extensive endogenous and exogenous interferences were evaluated and limits of quantification were identified empirically. Analytical ranges were 5-1,000 ng/mL for BUP and BUP-Gluc and 25-1,000 ng/mL for NBUP and NBUP-Gluc.

Validation and application of a method for the determination of buprenorphine, norbuprenorphine, and their glucuronide conjugates in human meconium.

A novel liquid chromatography tandem mass spectrometry method for quantification of buprenorphine, norbuprenorphine, and glucuronidated conjugates was developed and validated. Analytes were extracted from meconium using buffer, concentrated by solid-phase extraction and quantified within 13.5 min.

Excretion of methamphetamine and amphetamine in human sweat following controlled oral methamphetamine administration.

Background: Understanding methamphetamine (MAMP) and amphetamine (AMP) excretion in sweat is important for interpreting sweat and hair testing results in judicial, workplace, and drug treatment settings.

Methods: Participants (n = 8) received 4 10-mg (low) oral doses of sustained-release S-(+)-MAMP HCl (d-MAMP HCl) within 1 week in a double-blind, institutional review board-approved study. Five participants also received 4 20-mg (high) doses 3 weeks later.

Opioid disposition in human sweat after controlled oral codeine administration.

Background: Characterization of opioid excretion in sweat is important for accurate interpretation of sweat tests in drug treatment, criminal justice, and workplace drug testing programs.

Methods: Participants (n=20) received placebo, 3 low (60 mg/70 kg) or 3 high (120 mg/70 kg) codeine sulfate doses (used as a model for opioid excretion) within 1 week. Codeine and metabolites in sweat were collected with PharmChek Sweat Patches; hourly patches were applied for 1 to 15 h (n=775) and weekly patches for 7 days (n=118).

Disposition of cocaine and its metabolites in human sweat after controlled cocaine administration.

Background: Sweat testing is a noninvasive technique for monitoring drug exposure in treatment, criminal justice, and employment settings.

Methods: We evaluated cocaine excretion in 9 participants' sweat after they received 3 low doses (75 mg/70 kg) of cocaine HCl subcutaneously within 1 week and, 3 weeks later, 3 high doses (150 mg/70 kg). Six additional participants completed portions of the study.

Performance characteristics of the Cozart RapiScan Oral Fluid Drug Testing System for opiates in comparison to ELISA and GC/MS following controlled codeine administration.

Oral fluid is an interesting alternative matrix for drug testing in many environments, including law enforcement, workplace drug testing, and drug treatment facilities. Performance characteristics of the FDA-cleared, qualitative, Cozart RapiScan Opiate Oral Fluid Drug Testing System (Opiate Cozart RapiScan System or Opiate CRS) were compared to the semi-quantitative Cozart Microplate EIA Opiate Oral Fluid Kit (Opiate ELISA) and to gas chromatography/mass spectrometry (GC/MS). The following oral fluid opiate cutoffs were evaluated: the GC/MS limit of quantification (LOQ) of 2.