高效液相色谱法测定人血浆中氨溴素及药物动力学研究

Determination of ambroxol in human plasma by high performance liquid chromatography and its pharmacokinetics

目的：通过建立高效液相色谱法测定正常人口服盐酸氨溴素缓释胶囊后的血药浓度，以了解氨溴素的药物动力学行为。方法：血样经碱化后乙醚提取，盐酸反提后进样，以甲醇－０．０１ｍｏｌ／Ｌ磷酸盐缓冲液（ｐＨ７．３）－四氢呋喃（７０∶２７．５∶２．５，ｖ／ｖ）为流动相，利多卡因作为内标，在２４８ｎｍ处定量检测。结果：本法线性范围宽（１０～２００μｇ／Ｌ，ｒ＝０．９９９４），回收率稳定（８７．２±２．８）％，精确度高（日内ＲＳＤ≤４．１％，日间ＲＳＤ≤８．１％）。测定了健康受试者口服盐酸氨溴素缓释胶囊的血药浓度，并计算了相关的药物动力学参数。结论：应用本法可测定氨溴素血药浓度，可用作生物利用度研究，为临床合理用药提供参考。

Objectives: An accurate and sensitive assay for ambroxol in human plasma has been developed using reverse phase high performance liquid chromatography. Methods:Plasma samples were prepared for analysis by addition of internal standard lidocaine,alkalization with carbonate buffer(pH 10),extraction of diethyl ether and then followed by extraction with hydrochloric acid. An ALLTECH C 18 column, a methanol 0.01 mol/L phosphate buffer(pH 7.3) tetrahydrofuran mixture(70∶27.5∶2.5) as the mobile phase and the UV detector(set at 248 nm) were used. Results:The calibration curve was linear in the range from 10 μg/L to 200 μg/L with r =0.9994).The averaged recovery of ambroxol was 87.2 ± 2.8 %. The relative standard deviations for within day and between day were ≤4.1% and ≤8.1%, respectively. Following oral administration of 75mg ambroxol hydrochloride in volunteers, the peak levels of ambroxol in plasma averaged 163.1±16.6 μg/L at 3.9±0.3 h. Conclusions: This method was highly sensitive, specific, simple and rapid.