Driving under the influence of drugs (DUID) cases continue to challenge forensic toxicologists as both the volume and complexity of casework increases. Comprehensive DUID testing should also meet the drafted ASB/ANSI standard and the NSC-ADID recommendations. A simple method using protein precipitation followed by filtration extraction with an 8-minute run time by LC-MS/MS was developed, and a comprehensive ASB/ANSI validation performed. Assessed in blood quantitatively, and urine qualitatively, is 127 target drug and metabolite analytes including cannabinoids (12), amphetamines (11), cocaine and metabolites (6), benzodiazepines (36), Z-drugs (5), opioids (27), anticonvulsants (3), first-generation antihistamines (6), muscle relaxants (2), dissociatives and hallucinogens (6), barbiturates (10), and miscellaneous substances (3). Limits of detection are appropriate for DUID, and other forensic casework such as drug-facilitated crime (DFC) and postmortem investigations. To demonstrate applicability, 78 proficiency test blood and urine samples, and 1,645 blood and urine samples from authentic cases samples demonstrated effective detection of target analytes in forensic casework. By increasing the analytical scope of multiple drug classes via a single method, this technique detects drugs that may have previously gone undetected, such as flualprazolam, etizolam, mitragynine, gamma-hydroxybutyric acid, and psilocin, and improves laboratory efficiency by reducing the number of tests required. The described method is, to the authors’ best knowledge, the only published single procedure to meet all drugs listed in the drafted ASB/ANSI standard, and recommended Tier 1 and traditional drugs from Tier 2 for DUID screening, whilst also achieving many drugs recommended for DFC and postmortem testing.
The United States is observing higher rates of drug-related deaths than previously recorded [1]. Subsequently, mechanisms to process these and other death investigations at a faster rate are beneficial and in demand. The identification of common drugs of abuse and pharmaceutical drugs in biological specimens is routinely performed by forensic toxicology laboratories. However, a quick and straightforward method of drug screening carried out by the forensic pathologist during the autopsy may be warranted if immediate results are required to triage certain deaths, or if the forensic toxicology report is delayed. This may be especially desirable in jurisdictions with limited in-house toxicology capabilities. In this context, the usage of point-of-care (POC) urine drug screening tests may provide
Background: MDPV (3,4-methylenedioxypyrovalerone) is a synthetic stimulant that blocks transmitter uptake at transporters for dopamine and norepinephrine. Less is known about MDPV pharmacokinetics, especially with respect to brain concentrations of the drug and its metabolites. Objectives: The goal of the present study was: 1) to determine brain concentrations of MDPV and its metabolites, 3,4-dihydroxypyrovalerone (3,4-catechol-PV) and 4-hydroxy-3-methoxy-pyrovalerone (4-OH-3-MeOPV), after administration of MDPV, and 2) to relate brain pharmacokinetic measures to pharmacodynamic endpoints in the same subjects. Methods: Male Sprague-Dawley rats (300-400 g) received s.c. MDPV injection (1, 2, or 4 mg/kg) or its saline vehicle. Groups of rats were decapitated at 40 min and 240 min postinjection. Locomotor behavior was rated before decapitation, and the core temperature was obtained. Plasma and frontal cortex were analyzed to quantitate MDPV and its metabolites. Striatal samples were analyzed to measure dopamine, serotonin (5-HT), and their metabolites. Results: MDPV displayed brain-to-plasma ratios greater than 1 (range 8.8-12.1), whereas 3,4-catechol-PV and 4-OH-3-MeO-PV showed ratios less than 1 (range 0-0.3). MDPV increased behavioural scores reflective of locomotor stimulation at 40 and 240 min and produced slight hyperthermia at 240 min. MDPV had no effect on striatal dopamine but produced an increase in the metabolite homovanillic acid (HVA). Brain MDPV concentrations were positively correlated with behavioural scores and striatal HVA but not with other endpoints. Conclusion: The behavioural effects of MDPV are related to brain concentrations of the parent drug and not its metabolites. The modest effects of MDPV on monoamine systems suggest that other non-monoamine mechanisms may contribute to the effects of the drug in vivo.
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