Search

In Korea, an increasing number of people attempt to evade military conscription by posing as mental health patients. To verify the authenticity of mental illness, there is a need to detect wide range of psychoactive agents in biological specimens of conscription candidates. In this study, we developed and validated a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for simultaneous determination of 18 psychoactive agents and 6 metabolites in human plasma. The method was characterized by the use of a simple, fast and cheap protein precipitation as sample preparation, a rapid run time (11 min) and a low volume of plasma sample (200 μL). The analytes were monitored under the scheduled multiple reaction monitoring (sMRM) positive and negative mode using electrospray ionization (ESI). The essential validation parameters including selectivity, linearity, accuracy, precision, matrix effect and recovery were satisfactory. The limit of detection ranged from 0.0005 to 0.001 μg/mL, and limit of quantitation ranged from 0.005 to 0.025 μg/mL. The developed method was successfully applied to 323 actual plasma samples submitted by Korea central physical examination center of military manpower administration in 2016, and is expected to contribute to the rapid and accurate disposition of military service.

Phenylalkylamine derivatives, such as methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA), phentermine, fenfluramine, phendimetrazine, amfepramone, and ketamine, are widely abused recreational or anorectic drugs in Korea, and their abuse has become a serious social problem. Hair is a useful specimen to prove chronic use and liquid chromatography-tandem mass spectrometry (LC-MS/MS) has recently become a more popular tool for hair analysis due to sensitivity and simplicity in sample preparation. In order to overcome limitations of standard reversed-phase column to separate low molecular weight amines, we adopted a multi-mode reversed-phase column, Scherzo SS-C18, which was composed of strong ionic ligands and C18 ligands, and used pH gradient elution to separate seven psychotropic phenylalkylamines and their metabolites. The essential validation parameters including selectivity, LOD, LLOQ, linearity, intra- and inter-assay precision and accuracy, recovery, and the matrix effect were satisfactory. The LODs ranged from 0.1 ng/5 mg hair (diethylnorephedrine, fenfluramine, ketamine, and MA) to 0.5 ng/5 mg hair (amfepramone, MDA, phendimetrazine, and phentermine). The LLOQs were 1 ng/5 mg hair for all analytes. The developed method was successfully applied to determination of phenylalkylamines in authentic hair samples analyzed previously by a routine gas chromatography/mass spectrometry (GC–MS) method. A good correlation was observed between the two methods, with a slope near one.

Abuse of fluorinated synthetic cannabinoid analogs to avoid existing legal regulations has increased globally. The fluorinated JWH-122 analog, MAM-2201, was first reported in September 2012 as an ingredient in herbal mixtures in Korea. MAM-2201 is more potent than JWH-122 and a fatal intoxication case has been reported. In this study, we identified major MAM-2201 and JWH-122 metabolites from in vitro metabolism studies using human liver microsomes and compared the results with those of urine specimens from suspected MAM-2201 or JWH-122 users. MAM-2201 and JWH-122 produced common metabolites, N-5-hydroxylated, N-4-hydroxylated and carboxylated JWH-122 metabolites. Trace amounts of an N-4-hydroxylated MAM-2201 metabolite, a characteristic MAM-2201 metabolite, was detected in only a few urine specimens from MAM-2201 users. Both in vitro and in vivo studies demonstrated that N-5-hydroxylated JWH-122 metabolite was the primary metabolite of MAM-2201, whereas N-4-hydroxylated JWH-122 metabolite was predominant in JWH-122 metabolism. Based on these results, relative concentrations of N-5- and N-4-hydroxylated JWH-122 metabolites should be considered to verify MAM-2201 or JWH-122 users.

Due to their cannabis-like effects, synthetic cannabinoids have attracted much public attention since 2008. Thus, elucidation of the metabolic pattern and the detection of the intake of these drugs have been of major concern. In order to suggest appropriate urinary biomarkers to prove JWH-018 or JWH-073 intake, we selected the major metabolites of JWH-018 and JWH-073, namely (ω)-, (ω-1)-hydroxy, carboxy and 6-hydroxyindole metabolites, and validated a method for the quantification of these metabolites using solid-phase extraction based on LC-MS/MS analysis. Authentic urine specimens obtained from drug offenders were screened via a synthetic cannabinoid ELISA kit and were analyzed by LC-MS/MS for confirmation. Twenty-one out of a total of 52 samples (40%) were found positive for at least one metabolite of JWH-018 or JWH-073. N-pentyl hydroxy metabolites of JWH-018 and carboxy metabolites of JWH-018 and JWH-073 were detected in all positive samples. However, the rest of the metabolites were either not detected or only a small amount of them were found. A considerable variation was observed in the concentration ratio of (ω) and (ω-1)-hydroxy metabolites of JWH-018. Based on the results, it may have some pitfalls to determine the ingestion of specific synthetic cannabinoids by detecting a few metabolites, considering the continuous emergence of structurally related synthetic cannabinoids. Thus, use of synthetic cannabinoids should be proven carefully through comprehensive investigation of analytical results of biological specimens.