Reinventing quaaludes: a comprehensive review of designer methaqualone analogs.

Abstract

Purpose: The continuous emergence of NPS has posed a persistent challenge to forensic toxicology for more than a decade. Each year, previously unrecognized compounds appear on the illicit drug market, complicating analytical identification and increasing the risk of severe intoxications. The purpose of this study was to identify designer methaqualone analogs emerging in recent years and summarize available toxicological data in a comprehensive narrative mini review.

Methods: Online databases including PubMed, Google Scholar and early warning systems were systematically searched for reports on newly emerging designer methaqualone analogs. In addition, online forums were reviewed to collect information from recreational drug-users on psychoactive effects, effective doses, and routes of administration.

Results: The review summarizes metabolism of designer analogs and all reported intoxication cases, including concentrations found. Analytical aspects relevant to forensic practice are highlighted i.a. mass spectrometric characteristics (GC-EI-MS and LC-MS/MS with QqQ and QTOF instruments), differentiation of isomers, and stability in biological fluids and DBS cards over 365 days. Five newly emerging compounds, mephenoqualone, PPQ, PPTQ, Cl-PPQ, and MCPPQ, were identified on the illicit market. These substances have 100-fold higher potency than methaqualone and were described on online forums in late 2025.

Conclusions: Newly developed analogs are readily available online and represent serious and underrecognized threat due to their high potency and very low effective doses. Continued development of early warning systems and analytical methodologies is essential. Forensic toxicologists worldwide should be aware that these compounds may soon be encountered in seized materials and biological samples from intoxication cases.