2-Methyl-4'-(methylthio)-2-morpholinopropiophenone: A commercial photoinitiator being used as a new psychoactive substance.

Synthetic cathinones, which are novel psychoactive substances, have caused major social problems worldwide. A substance called 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MMMP), which is employed as a commercial industrial photoinitiator for triggering polymerization, has a basic cathinone backbone; however, few reports regarding MMMP have been published. In the current study, three potential metabolites of MMMP-namely hydroxy-MMMP (HO-MMMP), HO-MMMP-sulfoxide (HO-MMMP-SO), and HO-MMMP-sulfone (HO-MMMP-SO2)-were successfully synthesized, and MMMP and these three potential metabolites were used as standards to establish an analytic method based on liquid chromatography-tandem mass spectrometry for the quantitative analysis of urine. This analytic method and related parameters-including dynamic range, limit of quantification, selectivity, precision, accuracy, carryover effect, matrix effect, interference, and dilution integrity-were optimized and validated. Forty urine samples from 1,691 individuals who abused drugs were determined to contain MMMP, HO-MMMP, HO-MMMP-SO, or HO-MMMP-SO2; the results of this study indicate that approximately 2.37 % of drug abusers in Taiwan consumed MMMP in 2023. These 40 urine samples were analyzed to investigate the metabolism of MMMP in humans. The results indicate that HO-MMMP-SO is the main metabolite in human urine. This study recommends HO-MMMP-SO with a concentration of 2 ng/mL as a target and cutoff value, respectively, for identifying individuals who have consumed MMMP.

New ketamine analogue: 2-fluorodeschloro-N-ethyl-ketamine and its suggested metabolites.

Identifying new psychoactive substances (NPSs) and their metabolites is essential for regulating such substances for purposes of law enforcement and forensics. NPSs can be regulated on the basis of their chemical structures before they become a critical threat to society. Further, NPS metabolites can be targeted for analysis in urine, blood, and hair. This case study reports an incident in which 10 bags with approximately 15 g of crystalline material were seized from suspects by law enforcement officers and sent to the laboratory for confirmation. Gas chromatography-mass spectrometry, liquid chromatography-high-resolution mass spectrometry, and nuclear magnetic resonance (NMR) were employed to analyze these materials. The analyses revealed that the materials were a new ketamine analog, 2-fluorodeschloro-N-ethyl-ketamine (2-FDCNEK). Single-crystal X-ray diffraction (SXRD) analysis was also employed to confirm this result. In addition, metabolites of 2-FDCNEK were investigated using a fungal model and a urine sample from an abuser. The results suggest that 2-FDCNEK and 2-fluorodeschoro-norketamine are optimal metabolites for biological samples. This report presents the mass fragmentation, NMR analysis, and SXRD data of 2-FDCNEK. In addition, it provides suggestions regarding metabolites of 2-FDCNEK for law enforcement and forensic purposes, thereby facilitating the detection of this new ketamine analog.

Evaluation of the apolipoprotein E (apoE)-HDL-associated risk factors for coronary heart disease using duo-functional electrochemical aptasensor.

Apolipoprotein E containing high-density lipoprotein (apoE-HDL) and apoE-HDL cholesterol (apoE-HDL-C) are recently recognized as potential biomarkers for coronary heart disease (CHD). We herein developed a two-stage, enzyme-assisted, dual-signal aptasensor that enables a useful electrochemical sensing platform for simultaneous determination of apoE-HDL, apoE-HDL-C, and total HDL-C presented in the sample. The detection scheme consists of two subsystems. In subsystem (I), the level of apoE-HDL is evaluated upon the binding of apoE-specific aptamer and subsequently methylene blue (MB)-labeled DNA displacement occurs on the electrode surface, resulting in electrochemical reduction of methylene blue. In subsystem (II), two kinds of cholesterol levels (apoE-HDL-C and total HDL-C) can be measured. For apoE-HDL-C, the amount of cholesterol in apoE-HDL captured by the aptamer in the first step can be further determined with the aid of surfactant, cholesterol esterase, cholesterol oxidase, and p-aminophenol-mediated electrochemical signal amplification. As for total HDL-C, the amount of cholesterol is determined by the same approach as that used for apoE-HDL-C determination, but without washing (separation). The linear dynamic range for apoE-HDL determination is from 1 to 100 mg/dL (R2 = 1.00). For cholesterol standards, the linear dynamic range is determined to be 0-250 mg/dL (R2 = 0.98). Finally, serial dilutions of purified human HDL preparations were examined using the newly developed aptasensor; the percentage of apoE-HDL-C to HDL-C was found to be ~10%, which correlated well with previously reported values. In conclusion, we successfully developed an electrochemical aptasensor that allows concurrent quantification of apoE-HDL, apoE-HDL-C, and HDL-C on the same platform, offering an efficient, convenient, and purification-free sensing strategy for predictive CHD biomarkers.

Identification of a novel norketamine precursor from seized powders: 2-(2-chlorophenyl)-2-nitrocyclohexanone.

The identification of new psychoactive substances (NPSs) and their precursors is crucial to understand trends in NPSs so that they can be regulated before they pose a serious threat to human health. In this case, 24 bags containing approximately 600 kg of yellow powder were seized; the smugglers had been monitored for 3 years by the officers of Taiwan's Ministry of Justice Investigation Bureau. A handheld Raman analyzer yielded a positive result for N-boc norketamine; thus, the seized powder was sent to this laboratory for confirmation through gas chromatography-mass spectrometry, liquid chromatographyhigh-resolution mass spectrometry, proton nuclear magnetic resonance (1H NMR), carbon-13 nuclear magnetic resonance (13C NMR), two-dimensional correlation NMR measurements (2D_COSY), heteronuclear single-quantum correlation NMR measurements (2D_HSQC), and single-crystal X-ray diffraction. This thermolabile powder was subsequently identified as 2-(2-chlorophenyl)- 2-nitrocyclohexanone (2-CPNCH), which can be employed as a precursor for the synthesis of norketamine and is available commercially. Norketamine has similar pharmacological effects to ketamine and phencyclidine but is not regulated in many countries. In this case report, mass fragments, 1H NMR, 13C NMR, 2D_COSY, and 2D_HSQC data of 2-CPNCH are presented; moreover, how criminals exploit the loopholes in the law for conducting unauthorized drug manufacturing is discussed.