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目的:利用LC-MS/MS法对盐酸肼屈嗪片剂中的主要杂质进行结构鉴定。方法:采用Agilent ZORBAX SB-CN色谱柱(4.6 mm×250 mm,5μm),以缓冲液(含十二烷基硫酸钠和溴化四丁基铵,用0.05 mol·L~(-1)硫酸调p H至3.0)-乙腈为流动相进行洗脱,对盐酸肼屈嗪片剂进行强制降解和稳定性研究;并建立新的挥发性流动相条件通过LC-MS和LC-MS/MS法对盐酸肼屈嗪片剂中的主要杂质进行结构鉴定。结果:盐酸肼屈嗪片剂在多种条件下的稳定性欠佳;共检测到5个主要杂质:1,2,4-三唑并[3,4-ɑ]酞嗪、3-甲基~(-1),2,4-三唑并[3,4-ɑ]酞嗪、肼屈嗪乳糖缩合物、酞嗪和1-氨基酞嗪,其中4个初步鉴定为盐酸肼屈嗪与辅料相互作用产生的物质。结论:本研究新建立的LC-MS/MS方法可用于盐酸肼屈嗪中有关物质检查,对完善质量标准,加强药品的质量控制具有积极意义。
OBJECTIVE: To identify the major impurities in hydralazine hydrochloride tablets by LC-MS / MS. METHODS: Agilent ZORBAX SB-CN column (4.6 mm × 250 mm, 5 μm) was used in this study. The buffer solution (containing sodium dodecyl sulfate and tetrabutylammonium bromide, with 0.05 mol·L -1 sulfuric acid Adjust pH to 3.0) - acetonitrile as the mobile phase elution, forced degradation and stability of hydralazine hydrochloride tablets; and the establishment of a new volatile mobile phase conditions by LC-MS and LC-MS / MS The main impurities in hydralazine hydrochloride tablets were identified. Results: The stability of hydralazine hydrochloride tablets was poor under various conditions. Five major impurities were detected: 1,2,4-triazolo [3,4-azulene] phthalazine, 3-methyl (-1), 2,4-triazolo [3,4-azulene] phthalazine, hydralazine lactose condensate, phthalazine and 1-aminophthalazine, of which 4 were initially identified as hydralazine hydrochloride and Materials produced by the interaction of excipients. Conclusion: The newly established LC-MS / MS method can be used for the determination of related substances in hydralazine hydrochloride, which is of great significance to improve the quality standards and enhance the quality control of drugs.