RP-HPLC法测定人血浆中奥美拉唑浓度及其在健康男性志愿者药代动力学研究

目的: 建立人血浆中奥美拉唑的含量测定方法, 用于其血药浓度测定并进行临床药代动力学研究。方法: 1 ml 血浆样品以二氯甲烷提取, 采用反相高效液相-二极管阵列检测器分离测定血浆中的奥美拉唑浓度。色谱条件:krumasil C18 柱(4.6 mm ×200 mm, 5 μm), 流动相为乙睛:三蒸水(含0.01mol·L^-1磷酸氢二钠, 三乙胺调pH 7.5) =45:55(v/v);流速:1.3 ml·min^-1, 检测波长302 nm, 进样量30μl。9 例健康志愿者单剂量口服40 mg 奥美拉唑肠溶胶囊, 用高效液相色谱法测定给药后不同时间点血浆中奥美拉唑的浓度, 计算其药动学参数。结果: 奥美拉唑在10 ~ 2 000 μg·L^-1浓度范围内呈良好的线性关系, 最低检测浓度为10 μg·L^-1。高、中、低浓度的方法回收率分别为92.35%、96.90%、100.04%, RSD 均小于15%。健康人体药动学研究证明, 奥美拉唑的药-时曲线符合一室模型。结论: 本方法灵敏度高、专属性强、准确、简便, 适用于奥美拉唑的人体药代动力学研究。

Determination of omeprazole concentration in plasma by RP-HPLC and its pharmacokinetics in healthy male volunteers

AIM: To establish a reversed phase high performance liquid chromatography (RP-HPLC) method for determination of omeprazole in human plasma and the pharmacokinetic study of omeprazole in 9 healthy volunteers. METHODS:The RP-HPLC method was used. The separation was carried out using krumasil C18 (4.6 mm ×200 mm, 5 μm) column with mobile phase of acetonitrile and 0.01 mol·L^-1 phosphate buffer (55:45, v/v).The pH of the water phase was adjusted to 7.5 with triethylamine at flow rate of 1.3 ml·min^-1.The detection wavelength for omeprazole was 302 nm.A single oral dose 40 mg of omeprazole was given to 9 healthy males.RESULTS: The linear range for omeprazole was 10-2 000 μg·L^-1 (r =0.9999).The quantitation limit for omeprazole was 10 μg·L^-1.The relative recoveries were 92.35%, 96.90% and 100.04%, and RSD for intra-day and inter-day were both less than 15%.The pharmacokinetic analysis of omeprazole was studied.It was found to be fit for a one-compartment openmodel.CONCLUSION: The method is sensitive, accurate and simple, and suitable for the study on pharmacokinetic of omeprazole in human.