LC-MS/MS法同时测定比格犬血浆中氯维地平及其主要代谢物的浓度  

Simultaneous quantification of clevidipine and its primary metabolite in beagle plasma using LC-MS/MS

作　　者：陈涛[1,2] 张素行 叶沛珍 张飞鹏 林丽珊 张科之 王来友[1] 

机构地区：[1]广东药科大学药科学院,广东省代谢病中西医结合研究中心,广东广州510006 [2]广东中西达一新药开发有限公司,广东佛山528000

出　　处：《中国临床药理学与治疗学》2016年第3期306-312,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：第46批教育部留学回国人员科研基金启动项目;广东省自然科学基金项目(S2013010015021)

摘　　要：目的：建立液相色谱-串联质谱法（LC-MS/MS）同时测定比格犬血浆中的氯维地平及其主要代谢产物去乙基非洛地平（H152/81）的方法,并将其应用于氯维地平脂肪乳注射液在比格犬的生物等效性研究中。方法：本实验采用尼莫地平作为内标,血浆样品采用蛋白沉淀处理,分析柱为Synergi Polar-RP C18色谱柱（80,4μm,50 mm×2.0 mm）,流动相为0.1%甲酸乙腈和10 mmol/L醋酸铵水溶液,采用梯度洗脱,使用电喷雾电离源（ESI）,采用MRM扫描方式进行分析。结果：氯维地平在1~200 ng/m L、去乙基非洛地平在5~1 000 ng/m L范围内线性良好（r〉0.995）。待测物的日内、日间精密度和准确度均符合生物样品分析的相关要求。血浆样品经历3次冷冻-解冻循环和-80℃放置27 d都是稳定的。结论：本方法适合用于氯维地平脂肪乳注射液的生物等效性研究。AIM： The liquid chromatography- tandem mass spectrometry （LC-MS/MS） method was developed for simultaneous determination of cle- vidipine and its primary metabolite desethylfelodip- ine in beagle plasma using nimodipine as internal standard （IS）, and the method was applied to the bioequivalence study of clevidipine lipid emulsion injection in beagle dog. METHODS： Plasma sam- ples were prepared by protein precipitation, and compounds were separated by Synergi Polar-RP Cls column （80A 4μm, 502.0 mm） with the mobile phase of 0.1% formic acid in acetonitrile and 10 mmol/L ammonium acetate in Water. Analytes were detected by multiple reaction monitoring （MRM） mode with an electrospray ionization （ESI）. RE-SULTS：The standard curves were demonstrated lin- ear in the range of 1-200 ng/mL for clevidipine and 5-1000 ng/mL for desethylfelodipine, respectively（ r 〉 0. 995 ）. Both the intra-day and inter-day preci- sion and accuracy were all within the acceptable cri- teflon of bioanalysis. The plasma samples were sta- ble after three freeze-thaw cycles and being stored at - 80℃ for 27 days. CONCLUSION： This method was suitable for investigating the equivalence of clev- idipine lipid emulsion injection in beagle dog.

关 键 词：氯维地平 去乙基非洛地平 LC-MS/MS 生物等效性 

分 类 号：R969.1[医药卫生—药理学]