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

## TL;DR

A new method using TD-ESI-MS/MS was developed to quickly detect drugs in hair samples, showing high accuracy and potential for forensic and public health use.

## Contribution

The study introduces a validated high-throughput TD-ESI-MS/MS method for drug screening in hair with rapid analysis and forensic applicability.

## Key findings

- TD-ESI-MS/MS achieved high sensitivity and specificity for 17 drugs in hair with 1 min per sample.
- Etomidate analogs were the most prevalent substances identified in the analyzed specimens.
- Polydrug use patterns were observed, including combinations of etomidate with amphetamines and other analogs.

## 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 (<19.3%), with matrix effects controlled to <19.6%. The TD-ESI-MS/MS method achieved an analysis time of 1 min per sample, enabling high-throughput screening with a sensitivity >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.