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,5 μm);内标:酮洛芬;流动相:乙腈-2 mmol·L-1 pH 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。
Abstract
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
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Key words
:HPLC-MS /
enantioselectivity /
transdermal patche /
flurbiprofen
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中图分类号：
R969.1
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参考文献
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脚注
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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
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