Wang C J, Tian Z, Reyes V, Lin C C
Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
J Pharm Biomed Anal. 1995 Feb;13(2):121-7. doi: 10.1016/0731-7085(94)00111-e.
SCH 40120 is a potent anti-inflammatory agent under development for the topical treatment of dermal inflammatory and allergic disorders such as atopic dermatitis, contact dermatitis and psoriasis. We have previously described a sensitive enzyme immunoassay (EIA) for SCH 40120 in unextracted human plasma to support clinical studies. However, severe cross-reaction with unknown metabolites was observed during validation using samples from rats dosed with 14C-SCH 40120. Therefore, a selective extraction procedure was developed to remove the unknown plasma metabolites of SCH 40120 prior to EIA quantitation. The modified EIA using extracted plasma was cross-validated with an LC method using plasma samples from dosed subjects (human and rat), thereby confirming the specificity of the assay. The EIA can reliably quantitate SCH 40120 in plasma samples from 100 pg ml-1 to 10 ng ml-1 with good linearity, accuracy and precision, and is suitable for pharmacokinetic studies in man.
SCH 40120是一种正在研发的强效抗炎剂，用于局部治疗皮肤炎症和过敏性疾病，如特应性皮炎、接触性皮炎和银屑病。我们之前描述了一种用于未提取人血浆中SCH 40120的灵敏酶免疫测定法（EIA），以支持临床研究。然而，在使用给予14C - SCH 40120的大鼠样本进行验证期间，观察到与未知代谢物存在严重交叉反应。因此，开发了一种选择性提取程序，以在EIA定量之前去除SCH 40120的未知血浆代谢物。使用提取血浆的改良EIA与使用给药受试者（人和大鼠）血浆样本的液相色谱法进行了交叉验证，从而证实了该测定法的特异性。该EIA能够可靠地定量血浆样本中浓度范围为100 pg ml-1至10 ng ml-1的SCH 40120，具有良好的线性、准确性和精密度，适用于人体药代动力学研究。
