醋酸环丙孕酮/炔雌醇复方片剂在人体的药代动力学

摘要

目的 建立人血浆中醋酸环丙孕酮的HPLC-ESI-MS测定方法和丹酰氯衍生化血浆中炔雌醇的HPLC-APCI-MS测定方法,测定女性志愿者口服复方醋酸环丙孕酮片1片后的药代动力学参数,并对受试制剂和参比制剂的生物等效性进行评价.方法 血浆样品中的炔雌醇以乙酸乙酯提取后,与丹酰氯发生衍生化反应,进行HPLC-APCI-MS分析,流动相为10 mmol·L-1乙酸铵缓冲液(1％甲酸)-甲醇(3:97).检测离子分别为m/z 530.3(炔雌醇的丹酰氯衍生物)、m/z 404.3(内标,对羟基联苯的丹酰氯衍生物).结果 在10.43～625.8 pg·ml-1范围内炔雌醇的丹酰氯衍生物与内标的丹酰氯衍生物峰面积比值与浓度呈良好的线性关系,最低定量限为10.43 pg·ml-1.结论 本实验建立的分析方法灵敏、准确、简便,且统计学结果表明两种制剂生物等效.%Objective To develop an HPLC-ESI-MS assay for rapid determination of cyproterone acetate in human plasma and develop an HPLC-APCI-MS assay for determination of ethinylestradiol after derivatization with dansyl chloride and investigate the pharmacokinetics and bioequivalence of two compound cyproterone acetate tablets (containing 2 mg cyproterone acetate and 35 μ g ethinylestradiol) in 20 healthy women volunteers.Methods For ethinylestradiol,after its being extracted with ethyl acetate,the residue was derivatived with dansyl chloride,and separated by HPLC on a reversed-phase C18 column with a mobile phase of 10 mmol · L-1 ammonium acetate buffer solution (1％ formic acid)-methanol (3:97).HPLC-APCIMS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 530.3 for 3-dansylethinylestradiol,m/z 404..3 for 4-dansyl-hydroxybiphenyl.Results For ethinylestradiol,calibration curves were linear over the range 10.43-625.8 pg · ml-1,the lower limit of quantification in plasma was 10.43 pg · ml-1.Conclusion The assay is proved to be sensitive,accurate and convenient.The two preparations were bioequivalent.