Simultaneous determination of methamphetamine, MDMA, and ketamine and their metabolites in urine using a rapid and simple HS-SPME-GC-MS method: A forensic study on drug abuse patterns in South Korea.

The increasing abuse of stimulants such as methamphetamine (MA) and 3,4-methylenedioxy-methamphetamine (MDMA), along with the dissociative anesthetic ketamine (KET), poses a significant challenge in forensic toxicology in South Korea. To improve forensic toxicology analysis of polydrug use, a rapid and reliable method was developed for the simultaneous detection of MA, MDMA, KET, and their metabolites in urine using headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS). The method was optimized to enhance extraction efficiency while minimizing carry-over. Validation showed excellent linearity (R > 0.99), acceptable limits of detection (5-20 ng/mL) and quantitation (10-50 ng/mL), satisfactory precision and accuracy. Analysis of 95 authentic urine samples revealed widespread polydrug use, with 32 of 72 MDMA- or KET-positive cases testing positive for both substances. The metabolite-to-parent drug ratio of NKET/KET was significantly higher than that of AM/MA and MDA/MDMA, suggesting faster metabolism of KET. The validated HS-SPME-GC-MS method provides a reliable, solvent-free, and high-throughput approach for detecting MA, MDMA, and KET in forensic urine analysis. The findings highlight the prevalence of MDMA-KET co-ingestion in South Korea's club scene and emphasize the need for improved monitoring of polydrug abuse.