第 52 卷第 2 期 Vol. 52 No. 2 2022 年 4 月 Apr 2022

所属栏目：分析与测试 GC-MS测定磷酸西格列汀中基因毒性杂质水合肼

李善金1，徐 盼1，杨汉跃2，程青芳1* （1. 江苏海洋大学 药学院，江苏 连云港 222005；2.江苏德源药业股份有限公司，江苏 连云港 222047）

摘　要：建立了GC-MS测定磷酸西格列汀中基因毒性杂质水合肼含量的检测方法。采用DB-1701（14%-氰丙基-苯基）甲基聚硅氧烷毛细管柱进行检测，醋酸中通过丙酮衍生化处理，在全扫描模式下确定水合肼衍生物的定量离子m/z 为97。结果显示，水合肼衍生物在10.36~230.25 ng/mL浓度范围内线性关系良好，相关系数r=0.999 1；水合肼衍生物的定量限、检测限分别为10.4、3.1 ng/mL。平均加标回收率为102%~112%，RSD≤3%（n=12），系统适用性溶液25 ℃放置24 h内稳定，RSD≤6%，上述方法用于检测3批磷酸西格列汀样品，均未检出水合肼衍生物。所建立分析方法灵敏度高、专属性强，适用于磷酸西格列汀中基因毒性杂质水合肼的测定。

关键词：磷酸西格列汀；GC-MS；基因毒性杂质；水合肼；衍生化

中图分类号：TQ460.7　　文献标识码：A　　文章编号：1009-9212（2022）02-0064-05

Determination of Genotoxic Impurity Hydrazine Hydrate in Sitagliptin Phosphate by GC-MS

LI Shan-jin1, XU Pan1, YANG Han-yue2, CHENG Qing-fang1* (1. School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, China; 2. Jiangsu Deyuan Pharmaceutical Co., Ltd., Lianyungang 222047, China)

Abstract：A GC-MS method was established for the determination of the genotoxic impurity hydrazine hydrate in Sitagliptin Phosphate. The detection was performed on DB-1701 (14%-cyanopropyl-phenyl) methyl polysiloxane capillary column. The quantitative ion m/z 97 was scanned in the full scanning mode by derivatization using acetone and glacial acetic acid. The results showed that the hydrazine hydrate derivative in a test concentration range between 10.36 ng/mL to 230.25 ng/mL had good linear relationship (r=0.999 1). The quantification and detection limits of the hydrazine hydrate derivative were 10.4 ng/mL and 3.1 ng/mL respectively. The average recovery of the hydrazine hydrate derivative was 102%~112% , and a RSD (n=12) was less than 3%. The solution used in the system was stable at 25 ℃ for 24 h with a RSD of less than 6%. The above method was applied in the detection of three Sitagliptin Phosphate samples, and hydrazine hydrate derivative was not detected. The established method is suitable for the determination of genotoxic impurity hydrazine hydrate in Sitagliptin Phosphate with high sensitivity and good specificity.

Key words：Sitagliptin Phosphate; GC-MS; genotoxic impurity; hydrazine hydrate; derivatization

基金项目：连云港高新区科技计划项目（ZD201917）。

作者简介：李善金（1997—），男，江苏南京人，硕士，研究方向：药物分析与质量研究（E-mail：1325816338@qq.com）。

联 系 人：程青芳，教授，研究方向：制药工程方面的教学与研究（E-mail：489417058@qq.com）。

收稿日期：2021-11-17