LC-MS/MS测定人血浆中石杉碱甲的浓度及相对生物利用度

 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AUC_0→t分别为:(1384.079±325.094),(1479.165±288.738)μg·h·L^-1;ρ_max分别为:(3.062±0.821),(3.558±0.973)μg·L^-1;t_max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AUC_0→t计算为(94.4±18.7)%;以ρ_max计算为(86.3±15.4)%。统计学结果表明,两种制剂生物等效。

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

OBJECTIVE To study the pharmacokinetics and bioequivalence of huperzine A in human after oral administration using a simple LC-MS/MS method. METHODS Plasma was extracted with ethyl acetate after 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(ρ_max), time for peak concentration (t_max), AUC_0-t, and elimination half-life (t_1/2) 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 AUC_0-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^-1 respectively. ρ_max were (3.558±0.973) and (3.062±0.821)μg·L^-1.t_max 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 ρ_max. Formulation T is bioequivalent with Formulation R.