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

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC

ACS Applied Electronic Materials Pub Date : 2024-09-06 DOI:10.1016/j.jpba.2024.116459

Yanyan Jiang , Feng Zhou , Haihua Yao , Hong Wang , Hong Wu , Ye Huang , Mancang Gu

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Abstract

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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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

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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来源期刊

ACS Applied Electronic Materials Multiple-

CiteScore

7.20

自引率

4.30%

发文量

567