Antistasin(Merck Sharp & Dohme Corp.)

This study evaluates the presence of drugs of abuse (DOA) in blood from drivers suspected of driving under the influence of drugs (DUID) in the Netherlands from 2017 to 2023. After the introduction of new Dutch DUID legislation in July 2017, police officers were provided roadside oral fluid drug testers to establish suspicion of DUID. Since, there has been a steady and continuing increase in the number of apprehended DUID drivers. A large set of 64,116 blood samples was analysed for the following DOA: cocaine, THC, morphine, GHB and Amphetamine Type Substances (ATS: amphetamine, methamphetamine, MDMA, MDA, and MDEA), and compared with the Dutch legal limits. Most of the apprehended drivers were men (92 %), with a median age of 29 years. Of the analyzed blood samples, 65 % was found positive for one or more DOA. The most prevalent drug was THC (71 %), followed by amphetamine type substances (ATS, 30 %), cocaine (15 %) and GHB (6.8 %). Poly-drug use was found in 14 % of the samples, main combinations being THC with amphetamine or cocaine, and GHB with amphetamine. Factors contributing to negative blood results are, amongst others, the blood-oral fluid ratio, a time delay between oral fluid testing and blood sample collection and sending in samples despite a negative oral fluid test. THC was more common amongst younger drivers (under 26 years old), whereas cocaine and ATS use increased with age. The study presents important knowledge for both policymakers and DUID prevention specialists.

Designer precursors for the synthesis of amphetamine‐type stimulants pose a significant challenge to law enforcement. The precursors APAAN (α‐phenylacetoacetonitrile) and MAPA (methyl α‐acetylphenylacetate) became popular in the previous decade and have since been restricted. Recently, a ring‐substituted analog of MAPA used for the synthesis of MDMA (3,4‐methylenedioxymethamphetamine) was detected, highlighting the potential for criminal misuse of substituted analogs of these designer precursors. Previous research has characterized the impurity profiles of methamphetamine synthesized from APAAN and MAPA. In this study, the impurity profiles of MDMA and PMMA ( p ‐methoxymethamphetamine) synthesized from ring‐substituted analogs of APAAN and MAPA were characterized. In addition, byproducts forming from the conversion of p ‐methyl and p ‐fluoro analogs of APAAN and MAPA into analogs of P2P were investigated. MDMA was synthesized from 3,4‐methylenedioxy‐substituted MAPA (methyl α‐acetyl‐[3,4‐methylenedioxyphenyl]acetate, MAMDPA) via sodium cyanoborohydride reductive amination and hydrogenation with platinum oxide and methylamine. Four impurities originating from MAMDPA were detected in MDMA synthesized via reductive amination, all of which are 3,4‐methylenedioxy analogs of the impurities detected in methamphetamine synthesized from MAPA. Synthesis of MDMA via the hydrogenation route only produced one characteristic impurity, which, due to its instability under acidic conditions, is not likely to be present in clandestine MDMA hydrochloride samples. PMMA was synthesized via sodium cyanoborohydride reductive amination of MeO‐P2P produced from methoxyl‐substituted APAAN (α‐ p‐ methoxyphenylacetoacetonitrile, APMPAAN). Five impurities were identified as originating from APMPAAN, two of which are proposed to be the most reliable markers for the use of APMPAAN in the synthesis of PMMA.