基于LC-MS/MS法的盐酸肼屈嗪片有关物质研究
Study on the related substances in hydralazine hydrochloride tablets by LC-MS/MS
分类号：
出版年·卷·期（页码）：2016,36 (1):0-0
DOI:
10.16155/j.0254-1793.2017.01.01
-----摘要：-------------------------------------------------------------------------------------------
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AgilentZORBAX 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pH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。
-----英文摘要：---------------------------------------------------------------------------------------
Objective:To develop a new LC-MS/MS method for the identification of structures of the related substances in hydralazine hydrochloride tablets. Methods:Study on stability was carried out on an Agilent ZORBAX SB-CN column(4.6 mm×250 mm, 5μm)with a mobile phase consisting of acetonitrile and buffer(containing sodium laurilsulfate and tetrabutylammonium bromide, adjusting pH to 3.0 with 0.05 mol·L-1 sulfuric acid). Related substances were characterized by LC-MS and LC-MS/MS methods through a new volatile mobile phase in hydralazine hydrochloride tablets. Results:The stability of hydralazine hydrochloride tablets was undesirable under certain conditions. Five impurities were detected, including 1, 2, 4-triazolo[3, 4-ɑ] phthalazine, 3-methyl-1, 2, 4-triazolo[3, 4-ɑ]phthalazine, condensation of hydralazine and lactose, phthalazine and 1-amino phthalazine. Four of them were identified to be produced by interaction between hydralazine and excipients. Conclusion:The new LC-MS/MS method is proved to be effective in identification of the related substances in hydralazine hydrochloride tablets, which is useful for the drug quality control.
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