LC-MS/MS测定人血浆中石杉碱甲的浓度及相对生物利用度  

Determination of Huperzine A in Human Plasma by LC-MS/MS and Its Application to Relative Bioavailability of Huperzine A Tablets

作　　者：李芸霞[1] 蒋学华[1] 兰轲[1] 李晨睿[1] 

机构地区：[1]四川大学药学院临床药学与药事管理学系,成都610041

出　　处：《中国药学杂志》2009年第3期221-225,共5页Chinese Pharmaceutical Journal

摘　　要：目的建立人血浆中石杉碱甲浓度的LC-MS/MS测定方法,研究石杉碱甲在健康人体内的药动学行为,评价两种制剂的生物等效性。方法血浆样品经碱化后,乙酸乙酯提取,LC-MS/MS内标法分析。检测对象为石杉碱甲,m/z243/210,内标(磷酸可待因),m/z300/199。24名健康受试者交叉口服供试片和参比片,剂量均为0.4mg。结果石杉碱甲测定的线性范围为0.252～25.2μg·L-1;口服供试制剂和参比制剂后石杉碱甲的AUC0→t分别为:(1384.079±325.094),(1479.165±288.738)μg·h·L-1;ρmax分别为:(3.062±0.821),(3.558±0.973)μg·L-1;tmax分别为:(47.92±12.85),(44.17±20.62)min。结论本法灵敏、准确、简便。供试品的相对生物利用度为:以AUC0→t计算为(94.4±18.7)%;以ρmax计算为(86.3±15.4)%。统计学结果表明,两种制剂生物等效。OBJECTIVE To study the pharrnacokinetics and bioequivalence of huperzine A in human after oral administration using a simple LC-MS/MS method. METHODS Plasma was extracted with ethyl acetate aider the addition of the internal standard, codeine phosphate. The separation was achieved on a reversed- phase C18 column. Target ions were 243/210 for huperzine A and 300/199 for codeine phosphate. Twenty four healthy male volunteers received an oral dose of 0.4 mg huperzin A in a two treatment, open, crossover design. The plasma samples were collected for 15 h. Various pharmacokinetic parameters such as peak concentration （ρmax） , time for peak concentration （tmax）, AUC0→t, and elimination half-life （t1/2） were calculated for both of the two formulations. RESULTS The calibration curves were in the range of 0.252-25.2 μg.L^-1. The mean AUC0→t value for formulation R was found to be （ 1 479.165 ± 288.738 ） μg.h.L^-1 and that for formulation T was （ 1 384.079±325.094）μg.h.L^-1respectively. ρmax were （ 3.558 ±0.973） and （3.062±0.821） μg.L^-1. tmax were （44.17±20.62） and （47.92±12.85） min. CONCLUSION The relative bioavailability is （94.4± 18.7）% for AUC and （ 86.3 ± 15.4） % for ρmax. Formulation T is bioequivalent with Formulation R.

关 键 词：石杉碱甲 LC—MS/MS 血药浓度 药动学 生物利用度 

分 类 号：R969[医药卫生—药理学]