Key Points
- South Korea has faced large increases in drug use in recent years, most notably methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), and ketamine.
- Chromatographic techniques have been used to detect these drugs and their metabolites, but simultaneous analysis has not yet been researched.
- To rectify this, National Forensic Science researchers created a headspace solid-phase microextraction (HS-SPME)–solid-phase microextraction (SPME) technique for detecting the aforementioned drugs in body waste.
Researchers from the National Forensic Service in South Korea created a new method for detecting poly-drugs, such as methamphetamine and ketamine, based around headspace solid-phase microextraction (HS-SPME) and solid-phase microextraction (SPME). Their findings were published in the Journal of Chromatography B (1).
South Korea has faced huge increases in drug use in the past decade, with over 18,000 drug arrests being made in 2022 (2). Among the country’s cases of illicit substance usage, there is notable use of methamphetamine (MA), 3,4-methylenedioxy-methamphetamine (MDMA), and ketamine (KET). MA is a central nervous stimulant that increases alertness and energy, while also producing amphetamine as a major metabolite. MDMA, known as a stimulant with hallucinogenic properties, can result in euphoria and altered sensory perception. KET is a dissociative anesthetic with hallucinogenic effects
With MA, there has been a rapid rise in usage. It is estimated that socioeconomic losses from drugs were valued at $1.6 billion, with MA users in the country increasing by 50% from 2010 to 2021 (3). Due to the high prevalence of poly-drug abuse, simultaneous detection of MA, MDMA, and KET, alongside their metabolites, is vital for comprehensive toxicological analysis. Chromatographic techniques have been used to detect these drugs, but there is apparently no research on simultaneously analyzing these drugs and their metabolites. MDMA is frequently used alongside KET because users seek to counteract MDMA's overstimulation with KET's dissociative effects, transitioning from euphoria to detachment.
Many recent studies in this regard have used highly sensitive instruments, such as liquid chromatography-tandem mass spectrometry (LC–MS/MS). However, these efforts held risks of carry-over due to high drug concentrations in abusers’ urine. Gas chromatography–MS (GC–MS) is a widely used technique for analyzing MA, MDMA, and KET; compared to LC–MS/MS, GC–MS is less susceptible to matrix effects and instrument contamination from highly concentrated biological samples. However, GC–MS still requires extensive sample preparation and derivatization to enhance sensitivity, which can be time-consuming and labor-intensive.
In this study, headspace solid-phase microextraction (HS-SPME) was coupled with GC–MS to simultaneously detect MA, MDMA, KET, and their metabolites in urine. The method was optimized to enhance extract efficiency while minimizing risk of carry-over. It was also applied to 95 urine samples from suspected narcotics abusers, providing insights into the extent of poly-drug abuse in South Korea. Further validation showed excellent linearity (R2 > 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 provided 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, emphasizing the need for improved monitoring of polydrug abuse.
References
(1) Sim, J.; Kyung, S. Y.; Jo, J.; et al. 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. J. Chromatogr. B 2025, 1264, 124720. DOI: 10.1016/j.jchromb.2025.124720
(2) Kim, G. Understanding the Drug Crisis in South Korea: The Social and Regulatory Causes of the Problem. NHSJS 2025. https://nhsjs.com/2024/understanding-the-drug-crisis-in-south-korea-the-social-and-regulatory-causes-of-the-problem/ (accessed 2025-7-30)
(3) Im, C.; Kim, Y. Methamphetamine Spread in the Seoul Metropolitan Area: Geographical Random Forest Modeling Approach. Appl. Geogr. Stud. 2025, 174, 103470. DOI: 10.1016/j.apgeog.2024.103470