Current Issue : July-September Volume : 2025 Issue Number : 3 Articles : 5 Articles
Background/Objectives: Oxazolidinones are novel antimicrobial agents used to combat bacterial infections, particularly multidrug-resistant strains. However, the synthesis of oxazolidinone derivatives, such as linezolid, often involves the use of 3,4- difluoronitrobenzene (DFNB) as an initiator. Despite its effectiveness, residual DFNB in drug products raises significant health concerns due to its structural similarity to toxic and carcinogenic nitrobenzenes. This contamination is particularly concerning in pharmaceutical formulations, where it poses potential patient safety hazards. Therefore, strict concentration limits for this impurity are necessary. Methods: To ensure tight control of DFNB concentrations, this study established an 8.3 μg/g target limit. An advanced highperformance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to overcome current limitations in detecting trace DFNB. Under negative atmospheric pressure chemical ionization (APCI) conditions, DFNB exhibited characteristic ion formations, including [M]•− through electron capture and [M − F + O]− via substitution reactions. The quantitative method utilizes MS/MS ion transitions of the substitution product while optimizing chromatographic and spectrometric parameters to enhance both sensitivity and specificity. Conclusions: Validation tests confirm the efficiency, precision, and accuracy of this method, with a low limit of quantification (LOQ) of 5 ng/mL (0.83 μg/g). This technique enables accurate detection and quantification of DFNB in linezolid active pharmaceutical ingredient (API) and various formulations, providing a reliable tool for quality control. This method ensures the safe use of linezolid by effectively monitoring and minimizing the risks associated with DFNB contamination....
Background: Kukeya tablets (KYs), a traditional ethnic medicine prescription, are widely used to treat migraines and eye ailments in China. Despite their extensive clinical use, current knowledge on their therapeutic material basis is limited to a few major compounds, whereas certain minor ones have rarely been investigated. This study was conducted to screen and characterize the chemical components of KYs. Methods: A rapid and effective UHPLC-Q-Orbitrap-HRMS method was established. A mass spectrometry qualitative analysis strategy for KYs was developed, including in-house library matching, accurate molecular mass and elemental composition matching, and MS/MS fragmentation rule elucidation. Results: In total, 144 compounds were identified in KYs, including 36 anthrones and anthraquinones, 36 chromones, 25 triterpenes, 12 resin glycosides, 12 phenylpyrones, 10 phenolic acids, 4 flavonoids, 2 lignans, and 7 others. Meanwhile, the identified compounds were effectively classified into nine chemical classes. Among them, 11 compounds were identified for the first time and the identities of 22 compounds were accurately confirmed using reference substances. Conclusions: The results obtained benefit the understanding of the therapeutic basis of KYs, significantly promote the quality control of KYs, and elucidate potential effective components of other traditional medicines....
This study establishes and validates a novel ultra-high-performance liquid chromatography (UHPLC) method for the determination of urolithin A content in health products, a bioactive compound with potential anti-aging properties. Given the lack of standardized analytical methods for urolithin A in health products, this research addresses a critical gap in quality control. The method employs a methanol–water mobile phase, optimized gradient elution, and a specialized UPLC column (ACQUITY UPLC CSH Fluoro Phenyl) to achieve high resolution and specificity in the separation of urolithin A from its impurities. A variety of diluents, extraction solvents, and extraction times were tested to maximize analyte recovery and stability, with pure methanol yielding the highest recovery rate (over 95%) in 30 min. The method was validated in terms of linearity, sensitivity, repeatability, specificity, and precision. The calibration curve for urolithin A exhibited excellent linearity (r2 = 0.9998) over a concentration range of 0.100–10.000 μg/mL. Detection and quantification limits were found to be 0.051 μg/mL and 0.103 μg/mL, respectively. Precision testing revealed an inter-operator RSD of 1.3%, and recovery rates for spiked samples consistently fell within the 98–102% range. The developed method was successfully applied to analyze the urolithin A content in a commercially available health product, demonstrating its practicality for routine quality control. However, this method may currently be affected by the excipient matrix. This research contributes to the establishment of robust, reliable, and high-sensitivity analytical methods for the bioactive compounds found in health products, with significant implications for regulatory compliance and consumer safety....
A reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for simultaneous determination of triclabendazole (TCB) and ivermectin (IVM) in pharmaceutical dosage form. A mobile phase consisting of acetonitrile/water (50:50 v/v) with a flow rate of 1.5 mL/min was used for chromatographic separation of the mixture of TCB and IVM. The developed method was found to be linear with the correlation coefficient (r 0.999) for TCB and IVM in the presence of suspension. The limit of quantitation (LOQ), robustness, specificity, accuracy, and precision were validated for the developed method. The peak areas of five replicates of the samples were recorded, and the acceptance rate of suspension recovery was 98%. The intraday accuracies for TCB and IVM were 98.71% and 100.79%, respectively, with a relative standard deviation (RSD) of 0.87%. The limits of detection (LOD) of TCB and IVM were 0.058 mg/mL and 0.112 μg/mL, respectively, while the LOQ of TCB and IVM were 0.178 μg/mL and 0.340 μg/mL, respectively. The method’s % RSD for intra- and interday precision was deemed satisfactory. The developed method could be utilized for the determination and measurement of TCB and IVM in other samples....
Background: Inhibitors of cyclin-dependent kinases (CDKs) and epigenetic modifier enhancer of zeste homolog 2 (EZH2) have emerged as promising options in the pharmacotherapy of malignant tumors. Recently, we demonstrated synergistic antitumor effects of the CDK4/6 inhibitor abemaciclib and the EZH2 inhibitors GSK126 or tazemetostat in patient-derived glioblastoma (GBM) models. Importantly, all three drugs are substrates of the two most important plasma membrane multidrug transporters ABCB1 and ABCG2, with abemaciclib and tazemetostat also being inhibitors of these proteins. Methods: To investigate whether increased intracellular accumulation of either of the two drugs used in combination could have contributed to corresponding synergisms, we developed a simple LC-MS/MS method for simultaneous detection of the three substances in cell culture lysates. The method was validated in accordance with the current International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guideline M10 on bioanalytical method validation and study sample analysis. Results: All acceptance criteria were met. Subsequent analysis of intracellular drug concentrations confirmed increased cellular uptake of tazemetostat in the presence of abemaciclib in both GBM cell lines studied compared to single agent treatment. A comparable pattern was also observed for GSK126, but in only one of the two cell lines used. Conclusions: In conclusion, the observed synergistic antitumor effect could be partly due to increased intracellular accumulation, although this alone is certainly not sufficient to explain it. Overall, the developed method provides a valuable approach for characterizing interactions at the transport level and for predicting the efficiency of both anticancer substance classes in different cell lines....
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