Comprehensive evaluation of drug cases in Seoul and its metropolitan areas - 2022.

In order to prepare a response strategy for future drug analyses, the number and results of drug cases handled by the Seoul Institute of National Forensic Service were comprehensively evaluated, with a focus on Seoul and its metropolitan areas. In 2022, the Seoul Institute received approximately 12,150 requests for drug testing related to drug abuse and possession, and the urine samples were tested for approximately 16,000 drug species. The most frequently requested test was for cannabis (Δ-9-THC and Δ-8-THC), followed by methamphetamine, MDMA, ketamine, and synthetic cannabinoids. ADB-5'Br-BUTINACA and propyl butylone were newly emerging substances in 2022. These results were consistent with the main drug detection findings of the confiscated materials. During this period, 24 cases of drug-related deaths were reported, of which 6 were suspected to be the result of acute overdose poisoning caused by methamphetamine, MDMA, fentanyl, and heroin. In addition to the controlled substances regulated by the Narcotics Control Act, new psychoactive substances are being found to be circulating, and various measures are required to address this issue. This study is expected to improve future drug analyses methods and assist in establishing drug policies, and responding to future investigations.

Detection of l-Methamphetamine and l-Amphetamine as Selegiline Metabolites.

Selegiline (SE) is a selective, irreversible monoamine oxidase-B inhibitor, used for reducing symptoms in early-stage Parkinson's disease. The metabolites of SE include l-methamphetamine, l-amphetamine and desmethylselegiline (DSE). The stereoisomers of SE metabolites, d-methamphetamine and d-amphetamine are highly addictive psychostimulants and some of the most abused drugs in South Korea. In order to differentiate medical SE users form illicit methamphetamine abusers, it is important to distinguish between the l-isomers and d-isomers in urine samples. A 52-year-old male, seemingly under the influence of intoxication and demonstrating abnormal behavior, was reported to the police. The initial urine test using a methamphetamine detection kit demonstrated a positive result. Given the initial results, the police officer requested a further analysis of the urine sample. The urine sample was screened using headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). Both methamphetamine and amphetamine were detected, in addition to SE and DSE. To quantitate methamphetamine and amphetamine by HS-SPME-GC-MS, we performed a standard addition method due to the matrix effect of the case sample. Consistent with previous studies, our results indicated that the ratio of amphetamine to methamphetamine was 0.27, which was in the range of SE ingestion. Furthermore, we confirmed l-methamphetamine and l-amphetamine by chiral derivatization using (R)-(-)-α-methoxy-α-(trifluoromethyl) phenylacetyl chloride.

Determination of Nicotine, Cotinine and Trans-3'-Hydroxycotinine using LC/MS/MS in Forensic Samples of a Nicotine Fatal Case by Oral Ingestion of e-cigarette Liquid.

Nicotine is a potent neurotoxin alkaloid and is used in e-cigarette liquid. The LC/MS/MS method was linear over 0.01-1.0 mg/L (r2 = 0.992-0.995). Limit of detection and limit of quantitation were 0.001 mg/L (S/N = 3) and 0.003 (S/N = 10). The inaccuracy and imprecision were <13.2%. The recoveries were >99.3%. A 39-year-old dentist was found dead lying on the floor under the couch in his dental clinic. The concentration of nicotine, cotinine, and trans-3'-hydroxycotinine (heart blood/peripheral blood) was analyzed as follows: 87.2/85.2 mg/L (ratio 1.0), 1.4/1.1 mg/L (ratio 1.3), and 0.012/0.0089 mg/L (ratio 1.3), respectively. The concentration of nicotine was determined to be 6734.8 mg/kg in gastric contents and 7262.0 mg/L in remaining e-liquid. Only, high concentration of nicotine was detected in the gastric contents as well as the two pieces of evidence collected from the death scene. This fatal case resulted from oral ingestion of e-cigarette liquid. It is estimated that at least 714 mg of nicotine was orally ingested.

Simultaneous determination of five naphthoylindole-based synthetic cannabinoids and metabolites and their deposition in human and rat hair.

The continuing appearance of new synthetic cannabinoids has been a major issue in the field of forensic and clinical toxicology. In response to that, analytical methods for synthetic cannabinoids have been increasingly established in a variety of biological matrices. Since most of synthetic cannabinoids with structure similarity share some enzymatic metabolites, making the interpretation of analytical results and the discovery of the parent drug actually ingested very complicated, the investigation on metabolites of the first generation of synthetic cannabinoids with their relatively short side chains in chemical structure could be more important. Therefore, in the present study, we developed the analytical method for AM-2201, JWH-122 and MAM-2201 with JWH-018 as a precursor and their monohydroxylated metabolites in hair matrix. Also, using a rat model, AM-2201 and its monohydroxylated metabolites were identified and then the ratios of metabolite-to-parent drug were estimated to be used as criteria on external contamination. All analytes were extracted with methanol from washed and cut hair samples and the extracts were injected into LC-MS/MS with electrospray ion source in the positive ionization mode. Matrix effect and recovery were evaluated in hair matrices and no significant variations were observed. The validation results for precision and accuracy were satisfactory in both human and rat hair. The LOD and LOQ were 0.5 pg/10mg and 1.0 pg/10mg in human hair and 0.5 pg/20mg and 1.0 pg/20mg in pigmented and non-pigmented rat hair, respectively. Additionally, as a result of the animal study, there were not significant differences in the effect of pigmentation on the distribution of AM-2201 and its monohydroxylated metabolites in hair. Wide variations were observed for the concentrations of the naphthoylindole-based synthetic cannabinoids and metabolites in authentic hair samples from nine cases; those were 0.4-59.2 pg/mg for JWH-018, 0.1-0.8 pg/mg for JWH-073, 1.7-739.0 pg/mg for AM-2201, 0.1-402.0 pg/mg for JWH-122, 0.2-276.0 pg/mg for MAM-2201, 0.2-1.1 pg/mg for JWH-018 N-COOH, 0.3-37.2 pg/mg for JWH-018 N-5-OH, 0.3 pg/mg for JWH-073 N-COOH, 0.4 pg/mg for AM-2201 N-4-OH, 0.2-3.1 pg/mg for AM-2201 N-6-OHindole and 0.1-3.5 pg/mg for JWH-122 N-5-OH. This quantitative LC-MS/MS analytical method for five naphthoylindole-based synthetic cannabinoids and their metabolites was very useful to be applied to authentic hair samples, of which their analytical results suggested the incorporation of synthetic cannabinoids in the hair matrix and provided the information on ingested parent drugs.

Laparoendoscopic single-site versus conventional laparoscopic-assisted vaginal hysterectomy for benign or pre-invasive uterine disease.

BACKGROUND: The aim of this study was to compare the surgical outcomes of laparoendoscopic single-site (LESS) versus conventional laparoscopic-assisted vaginal hysterectomy (LAVH) in patients with benign or pre-invasive uterine disease. METHODS: The surgical outcomes of patients who had tried either LESS or conventional LAVH for benign or pre-invasive uterine disease were retrospectively reviewed and compared. Postoperative pain was assessed using the Visual Analog Pain Scale every 8 h after surgery. RESULTS: In total, 503 and 543 patients tried LESS and conventional LAVH, respectively. Additional ports were required in thirteen (2.6 %) and one (0.2 %) LESS and conventional LAVH patients, respectively (P = 0.001). One patient in each group required conversion to laparotomy (0.2 vs. 0.2 %, P = 0.957). The demographic and clinicopathologic characteristics were similar between groups. There was no difference in operating time, estimated blood loss, perioperative hemoglobin level change, transfusion requirement, and perioperative complications. However, the LESS LAVH group showed a reduced length of postoperative hospital stay (2.1 vs. 2.5 days, P < 0.001), an increased percentage of patients discharged within 2 days of surgery (88.9 vs. 73.7 %, P < 0.001), significantly lower pain scores at 8, 16, and 24 h after surgery, and a decreased percentage of patients requiring additional analgesics (33.4 vs. 61.3 %, P < 0.001). CONCLUSIONS: LESS LAVH demonstrated comparable technical feasibility to conventional LAVH and was associated with less postoperative pain, a decreased need for postoperative analgesics, and decreased length of postoperative hospital stay.

Quantitative determination of 11-nor-9-carboxy-tetrahydrocannabinol in hair by column switching LC-ESI-MS(3).

Hair analysis has been regarded as an alternative method to urine analysis in forensic and criminal cases. Cannabis (marijuana) is one of the most widely used drugs in the world and it has been controlled in South Korea since 1976. Identification of 11-nor-9-carboxy-tetrahydrocannabinol (THCCOOH) in hair can be an important proof of cannabis use because it can exclude the possibility of passive cannabis smoke exposure. In this study, we described a quantitative method of THCCOOH in hair using simple liquid-liquid extraction (LLE), selective column switching liquid chromatography with electrospray ionization (ESI)-MS(3). For the column switching system three columns (precolumn, trap column and analytical column) were used. Valve switch from the precolumn to the trap column was set from 3.0 to 4.0 min because THCCOOH appeared around 3.5 min with this precolumn. After 4.0 min the valve was switched to the original position and the analytes in the trap column were eluted onto the analytical column. Resolution occurred in this column and eluted into the ESI-MS(3) system. The internal standard was THCCOOH-d3. We used ESI-negative-MS(3) transition of ions at m/z 343 to 299 to 245 (343/299/245) and m/z 346 to 302 to 248 (346/302/248) for quantification of THCCOOH and THCCOOH-d3, respectively. The validation results of selectivity, matrix effect, recovery, linearity, precision and accuracy, and processed sample stability were satisfactory. The limit of detection (LOD) was 0.05 pg/mg and the limit of quantification (LOQ) was 0.10 pg/mg. The range of concentration of THCCOOH from 98 authentic human hair was 0.13-15.75 pg/mg. This method was successfully applied in the analysis of authentic human hair samples.

Deposition of JWH-018, JWH-073 and their metabolites in hair and effect of hair pigmentation.

Analysis of drugs in hair is often used as a routine method to obtain detailed information about drug ingestion. However, few studies have been conducted on deposition of synthetic cannabinoids and metabolites in hair. The first purpose of this study was to establish and validate an analytical method for detection of JWH-018, JWH-073, and their metabolites in hair, by use of UHPLC-MS-MS, for forensic application. The second purpose was to investigate the distribution of synthetic cannabinoids metabolites in hair and the effect of hair pigmentation, by use of an animal model. For this, JWH-073 was chosen as a representative synthetic cannabinoid. Finally, the developed method was applied to hair samples from 18 individuals suspected of synthetic cannabinoids use. JWH-018, JWH-073, and their metabolites were extracted from hair with methanol. The extract was then filtered and analyzed by UHPLC-MS-MS with an electrospray ion source in positive-ionization mode. Validation proved the method was selective, sensitive, accurate, and precise, with acceptable linearity within the calibration ranges. No significant variations were observed when different sources of both human and rat hair were used. The animal study demonstrated that JWH-073 N-COOH M was the major metabolite of JWH-073 in rat hair, and hair pigmentation did not have a significant effect on incorporation of JWH-073 and its metabolites into hair. In the analysis of 18 authentic hair samples, only JWH-018, JWH-018 N-5-OH M, and JWH-073 were detected, with wide variation in concentrations.

Quantitative analysis of propofol-glucuronide in hair as a marker for propofol abuse.

The inappropriate or illegal use of propofol has recently come to the fore as a serious social issue in South Korea. Thus, in spite of its superior potency as a therapeutic drug, propofol was classified as a controlled drug under the purview of Narcotics Control Law in South Korea in February of 2011. Accordingly, the determination of propofol and/or its metabolites in biological specimens is required to prove ingestion. Therefore, to demonstrate chronic ingestion, a quantitative analytical method for propofol-glucuronide in hair was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This method was applied to measure propofol-glucuronide in hair samples from 23 propofol abuse suspects and in both pigmented and nonpigmented hair from rats which had ingested propofol. Propofol-glucuronide in hair was extracted in methanol and then filtered and analyzed by LC-MS/MS with electrospray ionization in negative mode. The validation results of selectivity, matrix effect, recovery, linearity, precision and accuracy, and processed sample stability were satisfactory. The limit of detection was 20 pg/10 mg hair and the limit of quantification was 50 pg/10 mg hair. The concentration range of propofol-glucuronide in hair segments from 23 propofol abuse suspects was shown up to 1,410 pg/mg. The animal study demonstrated that the presence of melanin did not affect the deposition of propofol-glucuronide in hair. Thus, we propose propofol-glucuronide in hair as a marker for propofol abuse. This method will be very useful for monitoring the inappropriate use of propofol for both legal and public health aspects.

Simultaneous analysis of synthetic cannabinoids in the materials seized during drug trafficking using GC-MS.

A rapid and simple gas chromatography-mass spectrometry (GC-MS) method was developed and validated to identify and quantify synthetic cannabinoids in the materials seized during drug trafficking. Accuracy and reproducibility of the method were improved by using deuterated JWH-018 and JWH-073 as internal standards. Validation results of the GC-MS method showed that it was suitable for simultaneous qualitative and quantitative analyses of synthetic cannabinoids, and we analyzed synthetic cannabinoids in seized materials using the validated GC-MS method. As a result of the analysis, ten species of synthetic cannabinoids were identified in dried leaves (n = 40), bulk powders (n = 6), and tablets (n = 14) seized in Korea during 2009-2012, as a single ingredient or as a mixture with other active co-ingredients. JWH-018 and JWH-073 were the most frequently identified compounds in the seized materials. Synthetic cannabinoids in the dried leaves showed broad concentration ranges, which may cause unexpected toxicity to abusers. The bulk powders were considered as raw materials used to prepare legal highs, and they contained single ingredient of JWH-073, JWH-019, or JWH-250 with the purity over 70 %. In contrast, JWH-018 and JWH-073 contents in the tablets were 7.1-13.8 and 3.0-10.2 mg/g, respectively. Relatively low contents in the tablets suggest that the synthetic cannabinoids may have been added to the tablets as supplements to other active co-ingredients.

Species identification of Papaver by metabolite profiling.

Papaver somniferum L. and Papaver setigerum D.C. are controlled as opium poppy in Korea because they contain narcotic substances such as morphine and codeine. It is one of the critical issues whether the plants similar to opium poppy in shape are controlled plants or not. There are more than 110 species in the genus Papaver worldwide and about 10 species in Korea. As the morphological features of some species are very similar and the alkaloid contents and the ratios among the major alkaloids vary even within the same species, it is often difficult to identify the exact species by the morphological features and/or major alkaloids analysis. To develop a new method that uses metabolite profiling for species discrimination between P. somniferum, Papaver rhoeas and P. setigerum, the gas chromatography/mass spectrometry (GC-MS) data of the alkaline extract were processed with in-house Microsoft Visual Basic(®) modules and the chemical information was analyzed through multivariate statistical analyses such as Hierarchical cluster analysis (HCA), principal component analysis (PCA) and discriminant analysis (DA). The GC-MS results combined with multivariate analysis demonstrated that the metabolite profiling was an efficient technique for the classification and this method will provide a powerful tool for the identification of Korean Papaver species.