高效液相色谱法测定人血浆中盐酸氨溴索的浓度及其药代动力学研究

目的 :建立测定盐酸氨溴索血药浓度的方法及进行人体药代动力学的研究。方法 :采用反相高效液相色谱法 ,色谱柱 :Phe nomenex C18 色谱柱 (5μm ,250mm×4 6mm) ,柱温 :室温 ,以乙腈 -甲醇 -0 01mol/L磷酸盐缓冲液 ( pH=7 0) -四氢呋喃 (35∶35∶27 5∶2 5v/v)为流动相 ,以西替利嗪为内标 ,流速1 5ml/min ,紫外检测波长242nm ,用盐酸氨溴索与内标的峰面积比进行定量。线性范围640～10μg/L ,最低检测浓度为5μg/L。对12名健康受试者单次口服90mg盐酸氨溴索片剂后的药代动力学进行研究。结果 :12名健康受试者的血药浓度数据经3p97拟合 ,符合血管外给药一室模型 ,AUC0～t 为 (2240 67±798 48) μg/(h·L) ,Cmax 为(253 17±65 11) μg/L ,Tpeak 为 (2 22±0 68)h ,T1/2ke 为 (4 18±1 27)h。结论 :方法简便 ,灵敏度和准确度较高 ,完全能满足人体内低浓度药物的测定及药代动力学研究的要求。

Determination of Ambroxol Hydrochloride in Human Plasma by HPLC and the Pharmacokinetic Study

OBJECTIVE:To develop a method for the determination of ambroxol hydrochloride in human plasma ard study the clinical pharmacokinetics METHODS:Chromatographic separation has been achieved on C18 column with acetonitrile-methyl alcohol-0 01mol/L phosphatic buffer(pH=7 0)-tetrahydrofuran(35∶35∶27 5∶2 5v/v)as the mobile phase Detection was at UV 242nm The standard curve of ambroxol hydrochloride was linear in the range of 640～10μg/L,The minimum detection concentration was 5μg/L This assay procedure has been applied to monitoring plasma levels of ambroxol hydrochloride in 12 healthy volunteers who received po administration of drug RESULTS:The drug concentration-time profile conformed to the one-compartment model The AUC0～t and Cmax were(2 240 67±798 48)μg/(h·L),and(253 17±65 11)μg/L,respectively Tpeak and T1/2ke were(2 22±0 68)h and (4 18±1 27)h, respectively CONCLUSION:The study will provide a simple method for the determination of the plasma levels of ambroxol hydrochloride