高效液相色谱法测定人血浆中帕瑞昔布和伐地昔布的浓度

High-performance liquid chromatography for determination of plasma concen-tration of parecoxib and valdecoxib in human

目的建立高效液相色谱法测定人血浆中前体药物帕瑞昔布及其产物伐地昔布的浓度。方法色谱柱为Diamonsil C18柱(150 mm×4.6 mm,5μm),柱温30℃,流动相为乙腈-水-磷酸(57∶43∶0.01,V/V/V),流速1.0 mL.min-1,检测波长240 nm;内标为塞来昔布。结果帕瑞昔布的线性方程为Y=0.017 8X-0.022 9(r2=0.999 9),线性范围为1～100 mg.L-1。伐地昔布回归方程为Y=0.315 2X-0.005 1,(r2=0.999 8),线性范围为0.05～5 mg.L-1。帕瑞昔布和伐地昔布日内及日间RSD均小于15%,回收率均大于85%。结论本方法灵敏度高、专一性好、操作简单,可同时检测血浆中帕瑞昔布和伐地昔布,能满足药动学研究需要。

AIM To establish high-performance liquid chromatography （HPLC） method for determi- nation of plasma concentration of prodrug parecoxib and its product valdecoxib in human. METHODS The chromatographic column of Diamonsil C18 was used （ 150 mm × 4.6 mm, 5 μm） and the column temperature was 30 ℃. The mobile phase was composed of acetonitrile-water-phosphate （57 ： 43 ： 0.01, V/V/V）, and the flow rate was 1.0 mL .min^-1. The detection wavelength was 240 nm. Internal standard was celecoxib. RESULTS The regression equation of parecoxib was Y = 0.017 8X - 0.022 9, and the linear range was 1 - 100 mg.L-1 （τ^2 = 0.999 9）.The regression equation of valdercoxib was Y = 0.315 2X - 0.005 1, and the linear range was 0.05 - 5 mg＇L-1 （τ^2 = 0.999 8）. The intra- and inter- day RSD of parecoxib and valdercoxib were less than 15%, and the recove-ries were both more than 85%. CONCLUSION The HPLC method established issensitive, specific, and simple, and can be used to detect plasma concentration of parecoxib and valdercoxib simultaneously detected. The method is suitable for application in pharmacokinetic study of parecoxib.