Case series involving the synthetic cathinones alpha-PHP, alpha-PiHP, MDPHP, and MDPiHP in forensic investigations

Abstract

Synthetic cathinones remain a prevailing group of novel psychoactive substances (NPS) on the recreational drug market. Among the NPS stimulant subclass are the pyrovalerone derivatives, which include alpha-pyrrolidinohexanophenone (alpha-PHP), alpha-pyrrolidinoisohexanophenone (alpha-PiHP), and their methylenedioxy variants, 3,4-methylenedioxy-alpha-pyrrolidinohexanophenone (MDPHP), and 3,4-methylenedioxy-alpha-pyrrolidinoisohexanophenone (MDPiHP). This study presents a validated liquid chromatography-tandem quadrupole mass spectrometry (LC-QQQ-MS) method that quantifies and chromatographically separates alpha-PHP and MDPHP from their structural isomers, alpha-PiHP and MDPiHP, respectively. Quantitation employed a four-point standard addition approach and sample preparation was performed using liquid-liquid extraction with borax buffer (100 mM, pH 10.4) and 70:30 (v/v) N-butyl chloride and ethyl acetate. The method was subsequently applied to analyze ten cases suspected of containing pyrrolidinohexiophenones. The case series revealed a wide range of alpha-PiHP concentrations, with considerable overlap between intoxication and fatal exposures, ranging between 0.3 and 840 ng/mL in postmortem blood, 2600 ng/mL in urine, 350 ng/mL in vitreous humor, and 88 ng/g in the liver tissue, which are aligned with previously published findings. Additionally, this case report describes the identification of MDPiHP alone in femoral blood, suggesting that it poses toxicological risks independent of its structural isomer MDPHP. We conclude that there is an increasing need to separate isomers, or if separation is not feasible, verifying and reporting potential isomeric co-elution to minimize misclassifying causality and ultimately improve toxicological interpretation relative to NPS-related intoxication and fatalities.