超临界流体色谱法分离测定布立西坦片中立体异构体杂质  

Separation and Detection of Brivaracetam and Its Stereoisomers in Brivaracetam Tablets by Supercritical Fluid Chromatography

作　　者：朱丽萍 张叶 乐健 金薇 ZHU Liping;ZHANG Ye;LE Jian;JIN Wei(NMPA Key Laboratory for Quality Analysis of Chemical Drug Preparations,Shanghai Institute for Food and Drug Control,Shanghai 201203,China)

机构地区：[1]上海市食品药品检验研究院,国家药品监督管理局化学药品制剂质量分析重点实验室,上海201203

出　　处：《中国药学杂志》2024年第21期2084-2090,共7页Chinese Pharmaceutical Journal

基　　金：上海市科委项目资助(22142201800)。

摘　　要：目的 建立一种超临界流体色谱法分离和测定抗癫痫药布立西坦片中立体异构体杂质。方法 采用硅胶表面涂敷直链淀粉-三(3,5-二甲基苯基氨基甲酸酯)手性色谱柱(CHIRALPAK AD,4.6 mm×250 mm, 10μm),以超临界二氧化碳-甲醇(90∶10)为流动相,背压为18 MPa,进样量为6μL,柱温为40℃,流速为2 mL·min^(-1),于205 nm波长处分离布立西坦及其3种立体异构体。结果 布立西坦与其3种立体异构体在10 min内分别被洗脱,相邻异构体之间的分离度均不小于2.8,布立西坦在0.01~0.5 mg·mL^(-1)内与峰面积呈良好线性关系,相关系数为0.999 8(n=8),立体异构体杂质A、B、C在0.005~0.5 mg·mL^(-1)内与峰面积呈良好线性关系,相关系数均为0.999 9(n=9)。布立西坦和3种异构体的检测限均为2μg·mL^(-1)[信噪比(S/N)=3],定量限均为5μg·mL^(-1)(S/N=10)。3种异构体的3个不同浓度水平的平均回收率分别为102.1%,105.8%和102.6%(n=9)。结论 与常规正相模式液相色谱方法相比,采用超临界流体色谱分离布立西坦及其3种异构体,可显著提高分离效率,缩短分离时间,绿色环保,可有效用于布立西坦片中各异构体杂质的质量控制。OBJECTIVE To develop a supercritical fluid chromatography method for separation of brivaracetam and its three stereoisomers.METHODS Brivaracetam and its three isomers were separated on a silica gel column coated with amylose-tris(3,5-dimethyl phenylcarbamate)(CHIRALPAK AD,4.6 mm×250 mm,10μm)and maitained at 40℃.The mobile phase consisted of a mixture of CO_(2) and methanol(90∶10).The flow rate was at 2.0 mL min^(-1),and the detection wavelength was set at 205 nm.The back pressure of SF-CO_(2) was set at 18 MPa,and the injection volume was 6μL.RESULTS Brivaracetam and its three isomers were separated successfully in 10 min with a resolution factor of 2.8,2.8 and 4.0,respectively.Brivaracetam exhibited a good linear relationship with peak area within the concentration range of 0.01-0.5 mg·mL^(-1)(r=0.9998,n=8).Isomer A,B,and C also exhibited a good linear relationship with peak area within the concentration range of 0.005-0.5 mg·mL^(-1)(r=0.9999,n=9).The detection limits of brivaracetam and its three isomers(S/N=3)were all 2μg·mL^(-1),and the quantitation limits(S/N=10)were all 5μg·mL^(-1).The average spiked recoveries of three isomers at three different concentration levels were 102.1%,105.8%and 102.6%,respectively(n=9).CONCLUSION Compared with conventional liquid chromatography,supercritical fluid chromatography can significantly improve the separation efficiency,shorten the separation time,and greatly reduce the amount of alkane organic solvents,which can be effectively used for the quality control of the isomer impurities in brivaracetam tablets.

关 键 词：布立西坦 对映异构体 立体异构体 超临界流体色谱 

分 类 号：R917[医药卫生—药物分析学]