对映体选择性HPLC-MS用于氟比洛芬贴剂药物动力学研究  

Establishment of Stereospecific Assay of Flurbiprofen by High-Performance Liquid-chromatographic Tandem-Mass Spectrometry and Its Application to Pharmacokinetic Study

作　　者：叶金翠[1] 韦阳[1] 俞文英[1] 孙莹莹[1] 陈姗姗[1] 沈正荣[1] 陈国神[1] 曾苏[2] 

机构地区：[1]浙江省医学科学院药物研究所,杭州310013 [2]浙江大学药学院,杭州310006

出　　处：《中国药学杂志》2013年第13期1099-1103,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(30901871);浙江省科技厅项目(2010F20019;2011C13003;2011F10048);浙江省医学重点学科群建设(XKQ-010-001);浙江省卫生高层次创新人才培养工程项目

摘　　要：目的建立氟比洛芬对映体选择性高效液相-质谱分析方法,用于其贴剂经兔皮肤吸收的药物动力学研究。方法 手性色谱柱:大赛璐Chiralpak AD-RH(4.0 mm×150 mm,5μm);内标:酮洛芬;流动相:乙腈-2 mmol·L-1pH 5.3醋酸铵溶液(50∶50,V/V)。血浆中的药物和内标以甲基叔丁基醚提取。结果 氟比洛芬对映体在2.0～1 000 ng·mL-1内,主药与内标峰面积比与血浆浓度呈良好线性关系,定量下限浓度2.0 ng·mL-1。检测方法日内平均回收率98.5%～103.8%,RSD<6.0%。在连续5 d内测定高、中、低3个对映体浓度的血浆样品,日内精密度RSD<5.8%,日间精密度RSD<5.0%。结论 建立的对映体选择性高效液相-质谱分析方法灵敏、准确、精密,成功应用于兔血浆中氟比洛芬对映体的定量测定。Objective To develop an enantioselective HPLC-MS-MS method for the pharmacokinetic study of flurbiprofen transdermal patches. Methods The analyte and internal standard, ketoprofen, were extracted from plasma by methyl tert-butyl ether, analyzed on a Chiralpak AD-RH column（4.0 mm×150 mm,5 μm）with mobile phase consisting of acetonitrile-ammonium acetate buffer solution（2 mmol·L-1 pH 5.3, 50∶50, V/V）, and detected with UV detector at 273 nm. Results The assay was linear over the concentration range of 2.0-1 000 ng·mL-1 and the intra- and inter-day precision over this range were not more than 5.8%. The limit of quantification in plasma was 2.0 ng·mL-1. Conclusion The method established here is accurate, precise, rapid, sensitive, and successfully applied to the enantioselective determination of flurbiprofen in the pharmacokinetic study of flurbiprofen transdermal patches in rabbits.

关 键 词：高效液相-质谱法 对映体选择性 贴剂 氟比洛芬 

分 类 号：R969.1[医药卫生—药理学]