Drug Testing and Analysis最新文献

Synthetic derivatives of phenylethanamine, specifically 2-(2,5-dimethoxyphenyl)-N-((2-substituted)benzyl)ethanamines, regularly appear on the global market of new designer drugs and have been reported to be associated with adverse effects in humans who consume them. At the same time, their positional isomers may lack psychoactive effects. These compounds are not currently regulated by legislation and could potentially be used for medical purposes in the future. Continuing the study of the properties of 2-(2,5-dimethoxyphenyl)-N-((2-substituted)benzyl)ethanamines with different substituents, a poorly studied series of 2-(dimethoxyphenyl)-N-(2-(trifluoromethoxy)benzyl)ethanamines (NBOMe(F)) with a trifluoromethoxy group (OCF₃) in the ortho-position of the N-benzyl fragment is of interest. Gas chromatographic analysis revealed the existence of a critical pair of isomers when using an HP-5 type column, the differentiation of which is difficult under varying temperature conditions of the column thermostat. Their separation was achieved on a DB-17MS column under isothermal conditions at a temperature of 210°C. A method using thin-layer chromatography for the differentiation of this critical pair of isomers is also proposed. Retention indices of the isomeric compounds of the NBOMe(F) series and their N-trifluoroacetyl derivatives have been determined, which can serve as an additional identification criterion for gas chromatographic analysis. It has been shown that differentiation of NBOMe(F) isomers using electron ionization mass spectra is only possible if the spectra of both the isomers themselves and their N-trifluoroacetyl derivatives, which exhibit significant differences, are recorded. As an alternative method for differentiating the isomeric compounds, an approach using high-performance liquid chromatography–tandem mass spectrometry, which does not require derivatization, is proposed.

MDMA, commonly known as “ecstasy,” is widely used in clubs and at festivals, earning its reputation as a “party drug.” The increasing demand for rapid on-site dose estimation of MDMA in tablets arises from the need of various stakeholders, including law enforcement, emergency services, and public health officials, to respond appropriately to potential public safety risks and incidents. This study evaluates the performance of two portable spectroscopic techniques (near-infrared [NIR] and Fourier-transform-infrared [FT-IR]) combined with chemometric modelling for estimating the MDMA dose in tablets. Ninety-eight seized tablets were measured on-site with both spectroscopic techniques and confirmed by the reference techniques: gas chromatography (GC) combined with a mass spectrometer (MS) and a flame-ionization detector (FID). Considering the correlation values (NIR: R² = 0.64 for indirect contact with intact tablets, 0.87 for direct contact with homogenized tablets; FT-IR: R² = 0.84) and the RMSEP values (NIR: 8.0 for indirect contact with intact tablets, 5.9 for direct contact with homogenized tablets; FT-IR: 5.4), both spectroscopic techniques provide a reliable dose prediction in comparison to the GC-FID results. Moreover, these devices are suitable for rapid on-site application. The instruments' choice depends on several factors, such as speed, safety measures, and laboratory support for modelling. However, determining the MDMA dose does not address all health risks. Other factors, such as the presence of low-dosed substances (undetectable on-site) and the combination of MDMA with other drugs and/or alcohol also play a significant role. Therefore, laboratory analysis remains essential for comprehensive safety assessment.

Pegmolesatide, a novel synthetic erythropoietin-mimetic agent, was developed by the Hansoh Pharmaceutical Manufacturing Company Ltd. (Jiangsu, China). In late 2023, it was approved in China for the treatment of anemia in both dialysis and non-dialysis patients with chronic kidney disease, with the advantages of reduced immunogenicity and extended duration of action. The aim of this study was to develop a strategy for detecting pegmolesatide in doping analysis. Here, we present a bottom-up nano-liquid chromatography–high-resolution tandem mass spectrometry approach for qualitative analysis of pegmolesatide using erythropoietin receptor coupled magnetic beads, followed by trypsinization and subsequent detection of characteristic peptides. Using full scan and data-dependent MS/MS (ddMS2) modes, two characteristic peptide segments of pegmolesatide were identified. An analytical method using product ion scan mode was developed to detect the identified characteristic peptides. Both peptide segments were analyzed for the initial testing procedure, whereas one characteristic peptide segment obtained from complete trypsinization was analyzed for the confirmation procedure. After full validation, the selectivity, reliability, limit of detection, limit of identification, carryover, and stability were evaluated. The results demonstrate that our developed method can be a fit-for-purpose analytical method for the antidoping of pegmolesatide.

An ultrahigh performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) system was established for the rapid screening of doping agents in Chinese traditional patent medicine (CTPM), aiming to enhance the prevention and control of doping risks associated with herbal medicines. Samples were extracted by ultrasonic extraction with acetonitrile, while oily CTPM samples were extracted with 80% acetonitrile in water and purified using a Captiva EMR General Pigmented Dry cartridge. The extraction was concentrated under nitrogen flow, and the residues were dissolved, filtered, and detected using a Thermo Scientific UHPLC-Q-Orbitrap HRMS system. Separation was performed on an Agilent Zorbax Eclipse C18 column at 40°C with an injection volume of 5 μL and a gradient elution of 10-mM ammonium formate solution (pH 3.6) and acetonitrile as the mobile phase. The subsequent analysis was conducted using dual electrospray ionization in the Full MS/data-dependent secondary mass spectrometry scan mode. The method covers a total of 303 substances from 12 categories. Over 95% of the targets had limits of detection at or below 50 ng·g⁻¹ or ng·mL⁻¹ in CTPM. The method was validated for qualitative identification, including assessments of specificity, sensitivity, robustness, extraction recovery, matrix effect, and precision. The applicability of the method was demonstrated by the successful detection of higenamine (54%), ephedrine (42%), strychnine (11%), and morphine (2%) in 100 authentic samples. This paper presents a method for the rapid screening of doping agents in CTPM with high resolution, accuracy, and retrospectivity, reducing the risks of herbal medicine-induced doping violations.

Since around 2021, products such as e-cigarette liquid cartridges, herbal products, and gummy products, claiming to contain tetrahydrocannabinol (THC) analogues, have been seen for sale on the internet. Recently, products claiming to contain other THC derivatives have appeared. In this study, we identified the ingredients in products distributed on the internet that claim to contain THC derivatives. The e-cigarette cartridge product analyzed in this study was obtained from Japan in September 2024. One milligram of the oil product was treated with 1 mL of acetonitrile under ultrasonication. The resulting solutions were used for gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–photodiode array–mass spectrometry (LC–PDA–MS) measurements. After isolating and purifying unknown components from the product, structural analysis was performed by measuring ¹H, ¹³C nuclear magnetic resonance (NMR) and various two-dimensional NMR (COSY, HMQC, HMBC, and NOESY) and LC with hybrid quadrupole time-of-flight MS. The analysis revealed that chlorinated HHCs (i.e., (9R)-2-chloro-HHC, (9S)-2-chloro-HHC, (9R)-4-chloro-HHC, (9S)-4-chloro-HHC, (9R)-2,4-dichloro-HHC, and (9S)-2,4-dichloro-HHC) were the major components, and chlorinated dihydro-iso-THCs (i.e., 10-chloro-dihydro-iso-THC, 8-chloro-dihydro-iso-THC, and 8,10-dichloro-iso-THC) were the minor components isolated and identified from the product. Furthermore, Δ⁹-THCB-O-butanoate, a compound in which the hydroxyl group at the C1 position of Δ⁹THCB was butanoylated, was detected.