LC-MS法测定人血浆中盐酸氨溴索颗粒浓度及生物等效性研究  

HPLC-MS Determination of Ambroxol Hydrochloride and Its Pharmacokinetics and Bioequivalence in Human Plasma

作　　者：陈琳[1] 高署[2] 李俊杰[1] 冯鸣燕[1] 周阳海[1] 杨杲岚[1] 

机构地区：[1]暨南大学附属第一医院药剂科,广州510630 [2]合肥合源医药科技有限公司,合肥230000

出　　处：《江西医学院学报》2006年第6期43-46,50,共5页Acta Academiae Medicinae Jiangxi

摘　　要：目的建立人血浆中盐酸氨溴索浓度的HPLC-MS方法，用以测定健康志愿者口服盐酸氨溴索颗粒后的血药浓度．估算受试制剂和参比制剂的药代动力学参数，评价两种制剂的生物等效性和相对生物利用度。方法血浆中加入内标红霉素后，乙醚提取．HPLC-MS分离一分析。色谱系统：Phenomenex Luna CN柱150mm×2．0mmI．D．3μm，甲醇：水（含0．1％甲酸）=46：54为流动相，流速0．2mL／min，柱温30℃。质谱检测方式：SIM。结果盐酸氨溴索线性范围为3．125-800ng／mL，最低检测浓度为3．125ng／mL，提取回收率78．374％～93．130％。测定22名健康志愿者单剂量交叉口服盐酸氨溴索颗粒（受试制剂）及盐酸氨溴索片（参比制剂）90nag后的血药浓度经时过程，受试制剂和参比制剂的主要药代动力学参数：Cmax294．075ng／mL和297．870ng／mL；Tmax1．705ng／mL和1．523ng／mL；t1／2 8．646h和9．495h，无显著差异；受试制剂的相对生物利用度为（103．2±38．4）％。结论本法专属、准确、灵敏。统计学结果表明受试制剂和参比制剂生物等效。Objective An HPLC-MS method was established for study of pharmacokinetics and bioequivalence of ambroxol hydrochloride in human body. Methods Torlamician was used as internal standard. Plasma samples were extracted with diethyl ether and determined by HPLC-MS. The separation was carried out on a Phenomenex Luna CN column（150 mm×2.0 mm I. D. 3 μm） at 30℃. The mobile phase which contained 0.1% of methanoic acid, was methanol-water（46 ： 54, v/v）, running at a flow rate of 0.2 mL/min. HPLC-MS was performed in the selected ion monitoring（SIM） mode. A randomized crossover design was performed in 22 healthy volunteers. In the two study periods,a single 90mg dose of test and reference was administered to each volunteer. Results The linear calibration curve was obtained in the concentration range of 3. 125-800 ng/ mL. The detection limit of ambroxol hydrochloride in plasma was 3. 125 ng/mL. The average recovery was more than 80%. Cmax of ambroxol hydrochloride in blood for the test and reference formulations are 294. 075 ng/mL and 297. 870 ng/mL;Tmaxl. 705 ng/mL and 1. 523 ng/mL;t1/2 8. 646 h and 9. 495 h. The relative bioavailability of the test formulation was（103.2±38. 4）%. Conclusion The method was proved to be sensitive, accurate and convenient. The two formulations were bioequivalent.

关 键 词：盐酸氨溴索 高效液相色谱-质谱法 血药浓度 生物等效性 

分 类 号：R97[医药卫生—药品]