Baumann A, Kulmann H, Gorkov V, Mahler M, Kuhnz W
Research Laboratories, Schering Aktiengesellschaft, Berlin, Germany.
Arzneimittelforschung. 1996 Apr;46(4):412-8.
Cyproterone acetate (CAS 427-51-0, CPA) is a steroid hormone with antiandrogenic and progestogenic properties, which has been used in the therapy of prostate carcinoma in men, and for the treatment of severe acne and hirsutism in women. The aim of the present study was to compare two equally sensitive analytical methods, a radioimmunoassay (RIA) and a gas chromatographic/mass spectrometric method (GC/MS), for the quantitative determination of CPA in human serum samples and to assess their suitability for bioequivalence trials. To this end, serum samples which had been collected during a study on the bioequivalence oaf two CPA-containing formulations (Androcur 100 and Androcur 50) were analysed using both methods. Basic pharmacokinetic parameters, like Cmax, tmax, t1/2 and AUC were calculated from each data set and corresponding parameters were compared by statistical methods. A comparison of the drug concentration-time curves obtained with both analytical methods revealed that in particular at later sampling times (48 to 120 h post dose) concentration values generated by RIA were slightly higher by about 20-40% than those measured with GC/MS. This indicates the presence of cross-reacting metabolite(s), most likely the 15 beta-hydroxy-cyproterone acetate. Accordingly, the values of Cmax, AUC(0-120 h) and AUC were overestimated by the RIA method by about 10-20%, 5% and 10%, respectively. However, there was a high correlation between corresponding parameters derived from RIA and GC/MS analysis. Although AUC values were slightly overestimated with the RIA method was used, this had no influence on the decision about bioequivalence because the mean ratio of the target variables Cmax and AUC was not affected. The variance of the pharmacokinetic parameters which is relevant for the bioequivalence test were even lower for RIA based values than those calculated after GC/MS analysis. In conclusion, it was found that although the GC/MS method is superior to RIA in terms of specificity, both methods were equally suited to demonstrate the bioequivalence of the two CPA-containing formulations. Thus, in future studies of this kind, the more simple RIA may be used instead of GC/MS.
醋酸环丙孕酮（CAS 427-51-0，CPA）是一种具有抗雄激素和孕激素特性的甾体激素，已用于男性前列腺癌的治疗以及女性重度痤疮和多毛症的治疗。本研究的目的是比较两种同样灵敏的分析方法，即放射免疫分析法（RIA）和气相色谱/质谱法（GC/MS），用于定量测定人血清样本中的CPA，并评估它们在生物等效性试验中的适用性。为此，使用这两种方法分析了在一项关于两种含CPA制剂（Androcur 100和Androcur 50）生物等效性的研究中收集的血清样本。从每个数据集计算基本药代动力学参数，如Cmax、tmax、t1/2和AUC，并通过统计方法比较相应参数。对两种分析方法获得的药物浓度-时间曲线的比较表明，特别是在较晚的采样时间（给药后48至120小时），RIA产生的浓度值比GC/MS测量的值略高约20-40%。这表明存在交叉反应代谢物，最有可能是15β-羟基醋酸环丙孕酮。因此，RIA方法分别高估了Cmax、AUC(0-120 h)和AUC的值约10-20%、5%和10%。然而，RIA和GC/MS分析得出的相应参数之间存在高度相关性。尽管使用RIA方法时AUC值略有高估，但这对生物等效性的判定没有影响，因为目标变量Cmax和AUC的平均比值不受影响。与生物等效性试验相关的药代动力学参数的方差，基于RIA的值甚至比GC/MS分析后计算的值更低。总之，发现尽管GC/MS方法在特异性方面优于RIA，但两种方法同样适合证明两种含CPA制剂的生物等效性。因此，在未来此类研究中，可以使用更简单的RIA代替GC/MS。
