利福平中基因毒性杂质的鉴定和定量分析开发并验证针对 1-氨基-4-甲基哌嗪的 LC-MS/MS 方法

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL Journal of pharmaceutical and biomedical analysis Pub Date : 2024-09-06 DOI:10.1016/j.jpba.2024.116459

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引用次数: 0

摘要

利福平是长期治疗结核病的必需品，由于其潜在的不良影响（包括诱变作用），需要严格控制非治疗性杂质。有关利福平中基因毒性杂质控制策略的报道十分有限。本研究介绍了一种从原料合成中识别潜在基因毒性杂质的分析方法。利用核磁共振、高分辨质谱（HRMS）和高效液相色谱（HPLC）确认了 25-脱乙酰基-23-乙酰基利福平基因毒性杂质的结构。根据国际协调理事会的指导方针（包括特异性、线性、检测和定量限、准确性、精确性和稳健性），建立并验证了检测另一种基因毒性杂质 1-氨基-4-甲基哌嗪的 HPLC-HRMS 方法。这些开发改进了利福平中基因毒性杂质的质量控制策略，确保了产品安全。

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Identification and quantitative analysis of genotoxic impurities in rifampicin: Development and validation of a targeted LC-MS/MS method for 1-amino-4-methylpiperazine

Rifampicin, essential for long-term tuberculosis treatment, requires rigorous control of non-therapeutic impurities due to their potential adverse, including mutagenic effects. Reports on control strategies for genotoxic impurities in rifampicin have been limited. This study introduced an analytical method to identify potential genotoxic impurities from the synthesis of raw materials. The structure of the 25-deacetyl-23-acetyl-rifampicin genotoxic impurity was confirmed using nuclear magnetic resonance, high-resolution mass spectrometry (HRMS), and high-performance liquid chromatography (HPLC). An HPLC-HRMS method was established and validated for detecting another genotoxic impurity, 1-amino-4-methylpiperazine, adhering to the International Council on Harmonization guidelines, which include specificity, linearity, detection and quantification limits, accuracy, precision, and robustness. These developments improve the quality control strategy for genotoxic impurities in rifampicin, ensuring product safety.

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来源期刊

Journal of pharmaceutical and biomedical analysis 医学-分析化学

CiteScore

6.70

自引率

5.90%

发文量

588

审稿时长

37 days

期刊介绍： This journal is an international medium directed towards the needs of academic, clinical, government and industrial analysis by publishing original research reports and critical reviews on pharmaceutical and biomedical analysis. It covers the interdisciplinary aspects of analysis in the pharmaceutical, biomedical and clinical sciences, including developments in analytical methodology, instrumentation, computation and interpretation. Submissions on novel applications focusing on drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling; drug-related aspects of analytical biochemistry and forensic toxicology; quality assurance in the pharmaceutical industry are also welcome. Studies from areas of well established and poorly selective methods, such as UV-VIS spectrophotometry (including derivative and multi-wavelength measurements), basic electroanalytical (potentiometric, polarographic and voltammetric) methods, fluorimetry, flow-injection analysis, etc. are accepted for publication in exceptional cases only, if a unique and substantial advantage over presently known systems is demonstrated. The same applies to the assay of simple drug formulations by any kind of methods and the determination of drugs in biological samples based merely on spiked samples. Drug purity/stability studies should contain information on the structure elucidation of the impurities/degradants.