布地奈德缓释片有关物质方法的建立及色谱-质谱结构鉴定  

Establishment of a method of the related substances of budesonide extended release tablets and identification by LC-MS

作　　者：丁亚婷 邱宏春 尹山 郑鑫 杭太俊[1] DING Ya-ting;QIU Hong-chun;YIN Shan;ZHENG Xin;HANG Tai-jun(China Pharmaceutical University,Nanjing 211198,China;Prinbury Biopharm Co.Ltd,Shanghai 201203,China)

机构地区：[1]中国药科大学药学院,南京211198 [2]普霖贝利生物医药(上海)研发股份有限公司,上海201203

出　　处：《药物分析杂志》2021年第10期1796-1805,共10页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立超高效色谱法(UPLC法)测定布地奈德缓释片有关物质,并用液相色谱-四极杆-飞行时间串联质谱(LC-Q-TOF/MS)鉴定未知有关物质结构。方法:采用UPLC法,使用Waters ACQUITY UPLC BEH C;(150 mm×2.1 mm,1.7μm)色谱柱,以乙腈-磷酸盐缓冲溶液为流动相,梯度洗脱,对布地奈德缓释片有关物质进行分离;使用挥发性条件通过高分辨Q-TOF/MS测定未知有关物质的准确质量和元素组成,解析鉴定有关物质结构。采用液相色谱方法,使用Thermo BDS Hypersil C;(250 mm×4.6 mm,3μm)色谱柱,以乙腈-乙酸铵缓冲溶液为流动相,梯度洗脱,对布地奈德强降条件下产生的有关物质进行分离。结果:采用UPLC法时,主成分布地奈德及各有关物质分离度良好,并鉴定出6个未知有关物质,有关物质1和2为非对映异构体,有关物质3和4为差向异构体,有关物质5和10分别为文献中报道的布地奈德17-酸和布地奈德17-酮。结论:本文建立的方法简便、准确,专属性强,可用于布地奈德缓释片的有关物质检测和质量控制。Objective:To establish and verify an UPLC method for related substances of budesonide extended release tablets and identified unknown related substances by LC-Q-TOF/MS.Methods:The separation was performed on a Waters ACQUITY UPLC BEH C;column(150 mm×2.1 mm,1.7μm)by linear gradient elution with a mobile phase consisting of acetonitrile-phosphate buffer.Volatile mobile phase was used for the determination of the accurate mass and elemental composition of parent ions of the product by Q-TOF/MS.The structures of the unknown related substances were then figured out through the elucidation of the fragment ions.The volatile separation was performed on a Thermo BDS Hypersil C;(250 mm×4.6 mm,3μm)by linear gradient elution with a mobile phase consisting of acetonitrile-ammonium acetate buffer.Results:Budesonide and its related substances could be separated well by UPLC.Six unknown related substances were identified.The unknow related substancecs 1 and 2 were identified as diastereomers.The unknow related substancecs 3 and 4 were identified as epimers,and the unknow related substancecs 5 and 10 were identified as budesonide 17-acid and budesonide 17-ketone having been reported before.Conclusion:The established method in this study is sample,accurate and specific for the examination and quality control of related substances of budesonide extended release tablets.

关 键 词：布地奈德缓释片 糖皮质激素 有关物质 超高效液相色谱 液相色谱-四极杆-飞行时间串联质谱 结构鉴定 

分 类 号：R917[医药卫生—药物分析学]