Organ distribution of diclazepam, pyrazolam and 3-fluorophenmetrazine

• Published in: Forensic science international Vol. 303; p. 109959
• Main Authors: Lehmann, Sabrina, Sczyslo, Alissa, Froch-Cortis, Judith, Rothschild, Markus Alexander, Thevis, Mario, Andresen-Streichert, Hilke, Mercer-Chalmers-Bender, Katja
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01-10-2019; Elsevier Limited
• Subjects: 3-FPM; Adult; Amphetamines; Asphyxia; Autopsies; Autopsy; Benzodiazepines; Benzodiazepines - analysis; Benzodiazepines - pharmacokinetics; Bile; Bile - chemistry; Blood; Blood levels; Body fluids; Body Fluids - chemistry; Brain Chemistry; Brain research; Caffeine; Designer Drugs - analysis; Designer Drugs - pharmacokinetics; Diazepam - analogs & derivatives; Diazepam - analysis; Diazepam - pharmacokinetics; Diclazepam; Drug dosages; Femur; Fluids; Forensic sciences; Forensic Toxicology; Gastrointestinal Contents - chemistry; Heart; Human tissues; Humans; Intoxication; Kidney - chemistry; Liquid chromatography; Liver; Liver - chemistry; Lorazepam; Lorazepam - analogs & derivatives; Lorazepam - analysis; Lorazepam - pharmacokinetics; Lung - chemistry; Male; Mass spectrometry; Mass spectroscopy; Metabolism; Metabolites; Muscles; Nordazepam - analogs & derivatives; Nordazepam - analysis; Nordazepam - pharmacokinetics; Organ distribution; Pericardial Fluid - chemistry; Pharmaceuticals; Phenmetrazine - analogs & derivatives; Phenmetrazine - analysis; Phenmetrazine - pharmacokinetics; Post-mortem redistribution; Postmortem Changes; Psoas muscle; Psoas Muscles - chemistry; Pyrazolam; QuEChERS; Skin; Solid phases; Stimulants; Stomach; Tandem Mass Spectrometry; Tissues; Urine; Organ distribution; Pyrazolam; Diclazepam; Post-mortem redistribution; 3-FPM; QuEChERS
• ISSN: 0379-0738; 1872-6283
• DOI: 10.1016/j.forsciint.2019.109959

•Poly-drug intoxication with designer benzodiazepines and designer stimulants.•Post-mortem redistribution of diclazepam (and its metabolites), pyrazolam and 3-fluorophenmetrazine (3-FPM).•Cardiac/peripheral blood ratios (C/P) of diclazepam (and its metabolites), pyrazolam and 3-fluorophenmetrazine (3-FPM).
The organ distribution of 3-fluorophenmetrazine (3-FPM), pyrazolam, diclazepam as well as its main metabolites delorazepam, lormetazepam and lorazepam, was investigated. A solid phase extraction (SPE) and a QuEChERS (acronym for quick, easy, cheap, effective, rugged and safe) - approach were used for the extraction of the analytes from human tissues, body fluids and stomach contents. The detection was performed on a liquid chromatography–tandem mass spectrometry system (LCMS/MS). The analytes of interest were detected in all body fluids and tissues. Results showed femoral blood concentrations of 10 μg/L for 3-FPM, 28 μg/L for pyrazolam, 1 μg/L for diclazepam, 100 μg/L for delorazepam, 6 μg/L for lormetazepam, and 22 μg/L for lorazepam. Tissues (muscle, kidney and liver) and bile exhibited higher concentrations of the mentioned analytes than in blood. Additional positive findings in femoral blood were for 2-fluoroamphetamine (2-FA, approx. 89 μg/L), 2-flourometamphetamine (2-FMA, hint), methiopropamine (approx. 2.2 μg/L), amphetamine (approx. 21 μg/L) and caffeine (positive). Delorazepam showed the highest ratio of heart (C) and femoral blood (P) concentration (C/P ratio = 2.5), supported by the concentrations detected in psoas muscle (430 μg/kg) and stomach content (approx. 210 μg/L, absolute 84 μg). The C/P ratio indicates that delorazepam displays susceptibility for post-mortem redistribution (PMR), supported by the findings in muscle tissue. 3-FPM, pyrazolam, diclazepam, lorazepam and lormetazepam did apparently not exhibit any PMR. The cause of death, in conjunction with autopsy findings was concluded as a positional asphyxia promoted by poly-drug intoxication by arising from designer benzodiazepines and the presence of synthetic stimulants.