HPLC手性固定相法测定患者血浆中布洛芬对映体的浓度

Determination of Ibuprofen Enantiomers in Plasma by HPLC-Chiral Stationary Phase

关键词:  高效液相色谱法  布洛芬  手性固定相  对映体

Key words:  HPLC  ibuprofen  chiral stationary phase  enantiomers

摘要:

目的 建立用高效液相色谱法测定血浆中布洛芬对映体浓度的方法。方法 用正己烷-异丙醇混合液(100∶5)提取血浆样品中布洛芬，在Chirobiotic V(250 mm×4.6 mm，5 μm)柱上，以甲醇-冰醋酸-三乙胺(100∶0.04∶0.02)为流动相进行分离，于226 nm 波长处检测，内标为吲哚美辛。结果 R-布洛芬、S-布洛芬和内标没有干扰，分离度良好。R-布洛芬和S-布洛芬血药浓度在0.01~5 mg·L^-1内线性关系良好。两个对映体相对回收率分别为99.1%~102.2%和99.3%~102.4%，绝对回收率分别为66.8~72.9和66.3~71.4，日内RSD分别为4.2%~5.4%和3.6%~5.1%，日间RSD分别为5.9%~7.3%和6.2%~7.9%。结论 该方法准确、快速、简便、灵敏度高、重复性好，可同时测量血浆中R-布洛芬和S-布洛芬的药物浓度，并可用于药动学参数的研究及患者血药浓度监测。

Abstract:

OBJECTIVE To establish a method for the determination of plasma levels of enantiomers of ibuprofen. METHODS Ibuprofen was extracted from samples with Hexane-isopropanol(100∶5). HPLC was performed on Chirobiotic column with methanol-aceticacid-triethylamine(100∶0.04∶0.02) as mobile phase. Detection wavelength was 226 nm. Indomethacin was used as the internal standard. RESULTS Under this chromatographic condition, R-ibuprofen, S-ibuprofen and indomethacin had no interference within each other. The calibration curve was linear in the range of 0.01-5 mg·L^-1 for R-ibuprofen and S-ibuprofen. The relative recoveries of R-ibuprofen and S-ibuprofen were 99.1%-102.2% and 99.3%-102.4% respectively. The absolute recoveries of R-ibuprofen and S-ibuprofen were 66.8-72.9 and 66.3-71.4 respectively; RSD range of intraday were 4.2%-5.4% and 3.6%-5.1%. RSD ranges of interday were 5.9%-7.3% and 6.2%-7.9% respectively. CONCLUSION This method is accurate, rapid, with high sensitivity and good repeatability. It is applicable for the determination and pharmacokinetic study of the enantiomers of ibuprofen in plasma.