醋酸卡泊芬净标准物质的研制

Establishment of national reference standard of caspofungin acetate

摘要

目的: 本研究成功研制出首批醋酸卡泊芬净国家标准物质,为相关原料和制剂的质量控制提供保障。方法: 综合采用高分辨质谱(HRMS)、核磁共振(NMR)、红外光谱(IR)等分析技术对醋酸卡泊芬净的结构进行确证,并对该化合物的核磁信号进行归属。采用质量平衡法(MBM)对醋酸卡泊芬净进行赋值,并利用核磁共振定量法(qNMR)和外标法(ESM)对上述结果进行佐证。结果: 本批醋酸卡泊芬净标准物质以C₅₂H₈₈N₁₀O₁₅·2CH₃COOH计,含量为97.0%。结论: 建立了首批醋酸卡泊芬净国家标准物质。

Abstract

Objective: This study successfully developed the first batch of national reference standards of caspofungin acetate to ensure quality control of related raw materials and finished products. Methods: The structure of the caspofungin acetate reference standard was confirmed by comprehensive analytical techniques including high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR), and infrared spectroscopy (IR), and the NMR signals of the compound were assigned. The content of caspofungin acetate was determined by the mass balance method (MBM), and the results were corroborated by quantitative nuclear magnetic resonance (qNMR) and the external standard method (ESM). Results: The content of this batch of caspofungin acetate reference standard, calculated as C₅₂H₈₈N₁₀O₁₅·2CH₃COOH, was 97.0%. Conclusion: The first batch of national reference standards of caspofungin acetate was successfully developed.

关键词

醋酸卡泊芬净 / 标准物质 / 质量控制 / 核磁共振定量法 / 质量平衡法

Key words

caspofungin acetate / reference standard / quality control / NMR / mass balance method

[1] 刘秀书, 邹爱英. 棘白菌素类抗真菌药临床应用研究进展[J]. 天津药学, 2014, 26(6): 70-72.
[2] 张诗琪, 程德云. 棘白菌素类抗真菌药物的临床应用进展[J]. 医学综述, 2020, 26(5): 986-990.
[3] 高志峰, 肖新月, 曹丽梅, 等. 国家药品标准物质一级直供的实施要点研究[J]. 中国新药杂志, 2021, 30(1): 13-16.
[4] MALZ F, JANCKE H. Validation of quantitative NMR[J]. J Pharm Biomed Anal, 2005, 38(5): 813-823.
[5] 陆天琪. 定量核磁内标候选物研究[D]. 天津: 天津理工大学, 2023.
[6] RUNDLÖF T, MATHIASSON M, BEKIROGLU S, et al. Survey and qualification of internal standards for quantification by 1H NMR spectroscopy[J]. J Pharm Biomed Anal, 2010, 52(5): 645-651.
[7] HOLZGRABE U. Quantitative NMR, methods and applications[M]//Encyclopedia of Spectroscopy and Spectrometry. Amsterdam: Elsevier, 2017: 816-823.
[8] 李香, 田光宗, 秦春君, 等. 肺炎球菌荚膜多糖中C多糖的定量1H-NMR和31P-NMR法测定[J]. 中国现代应用药学, 2025, 42(13): 2195-2202.
[9] 关皓月, 冯玉飞, 孙百浩, 等. 1-甲基-4-亚硝基哌嗪国家标准物质的研制及其核磁定量考察[J]. 中国现代应用药学, 2023, 40(24): 3399-3403.