A practical HPLC method using six polysaccharide-based chiral stationary phases with a single polar organic solvent mobile phase separated the enantiomers and regioisomers of 32 novel diphenidine-derived psychoactive substances. The cellulose tris(3-chloro-4-methylphenylcarbamate) coated on silica gave baseline separation for 25 of 26 monosubstituted diphenidines with resolution values above 1.5, and optimum separation for 21 of them (resolution 2.9–22.4). The chiral selector type and the substituent position on the 1-phenyl ring strongly influenced chiral resolution, with 4-position substituents showing greater discrimination than 2-position ones. Enantiomer elution order reversed for 2-methoxphenidine depending on the stationary phase. Analysis of real samples confirmed 2-methoxphenidine and diphenidine were traded as racemates, and common adulterants did not interfere.
5-MeO-MiPT is metabolized through multiple phase I and II pathways in both zebrafish and human liver microsomes. In zebrafish, six metabolites were identified, with N-Demethylation and Indole-hydroxylation as primary phase I reactions, and Glucoside conjugation and Sulfonation as phase II reactions. In human liver microsomes, nine metabolites were generated, including N-Demethylation, 5-O-Demethylation, N-Depropylation, N-Oxidation, Indole-hydroxylation, and combined reactions. Phase II metabolism in human microsomes involved Glucoside conjugation after Indole-hydroxylation or 5-O-Demethylation. Proposed markers for screening 5-MeO-MiPT intake include 5-MeO-MiPT-N-Demethylation, 5-MeO-MiPT-Indole-hydroxylation, and OH&Glucoside conjugation-5-MeO-MiPT, along with the parent drug.
A method for measuring MDMA content in ecstasy tablets using a compact 60 MHz benchtop NMR spectrometer was validated against UNODC guidelines. The method showed good specificity, selectivity, linearity, precision, and accuracy. Among seized tablets, the lowest MDMA free base detected was 9.35 mg in a piperazine mix, and the highest was 237.55 mg. The median MDMA amount in 2022 was 9.1% lower than pre-pandemic 2019 data but still higher than the 105 mg median reported in 2018. Within-batch variation was insignificant for one seizure but greater for another, indicating a single tablet's content may not represent the whole batch. The upward dosage trend underscores the need for ongoing monitoring and prevention interventions.