TD-ESI-MS/MS for High-Throughput Screening of 13 Common Drugs and 4 Etomidate Analogs in Hair: Method Validation and Forensic Applications.

A dual analytical workflow combining thermal desorption-electrospray ionization-tandem mass spectrometry (TD-ESI-MS/MS) for rapid screening and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for confirmatory quantification was developed to detect 17 psychoactive substances and metabolites in hair. The TD-ESI-MS/MS method showed limits of detection between 0.1 and 0.2 ng/mg, with 85.7% sensitivity and over 89.7% specificity. UPLC-MS/MS confirmation achieved accuracy rates of 89.7-99.8%. In analyzed specimens, etomidate analogs were the most prevalent psychoactive substances (73.6%), followed by amphetamine-type stimulants (12.5%), ketamine-type drugs (9.0%), and opioids (2.8%). Polydrug use patterns included concurrent etomidate-amphetamine consumption (n = 5) and complex analog combinations (etomidate-isopropoxate-metomidate, n = 13), indicating evolving abuse trends. The approach demonstrates viability for forensic and public health applications.

Study at a glance

Abstract

This study established a dual analytical workflow integrating thermal desorption-electrospray ionization-tandem mass spectrometry (TD-ESI-MS/MS) for rapid qualitative screening and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for confirmatory quantification of 17 psychoactive substances and metabolites across six classes (opioids, amphetamine-type stimulants, cocaine, ketamine-type drugs, cannabinoids, and etomidate analogs) in hair matrices. Validation of the TD-ESI-MS/MS method demonstrated its sensitivity (limits of detection: 0.1-0.2 ng/mg) and precision (85.7% and a specificity >89.7% for the 17 analytes. UPLC-MS/MS confirmation validated the screening results with accuracy rates of 89.7-99.8%. An analysis of specimens confirmed positive identified etomidate analogs as the predominant psychoactive substances (73.6%), with a lower prevalence of amphetamine-type stimulants (12.5%), ketamine-type drugs (9.0%), and opioids (2.8%). The polydrug use patterns identified concurrent etomidate-amphetamine consumption (n = 5) and complex analog combinations (etomidate-isopropoxate-metomidate, n = 13), suggesting evolving abuse trends. Despite limitations in the temporal resolution and representativeness of the cohort, this study demonstrated the viability of TD-ESI-MS/MS for bridging forensic and public health priorities. Future work should focus on optimizing the durability of the ion source for TD-ESI and validating this method across diverse populations to enhance its generalizability.