Wang C J, Tian Z, Gommoll C, Reyes V, Lin C C
Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, NJ 07033.
J Pharm Biomed Anal. 1993 Oct;11(10):871-9. doi: 10.1016/0731-7085(93)80043-z.
SCH 40120 is a potent acute anti-inflammatory agent under development for topical treatment of dermal inflammatory and allergic disorders such as atopic dermatitis, contact dermatitis and psoriasis. In order to support percutaneous absorption studies, a competitive enzyme immunoassay (EIA) was developed to determine SCH 40120 in unextracted plasma samples. SCH 38280, a carboxylated analogue of SCH 40120, was used as the hapten and conjugated with bovine thyroglobulin (Thy). The hapten-Thy conjugate was used as the immunogen to immunize rabbits for antibody production. The hapten was also coupled to horseradish peroxidase (HRP) to form SCH 38280-HRP, which was used as the tracer. The EIA can detect SCH 40120 concentrations as low as 50 pg ml-1 of plasma, and can reliably quantitate SCH 40120 in plasma samples from 100 pg ml-1 to 10 ng ml-1 with good linearity, accuracy and precision. A variety of structurally related compounds and potential metabolites did not significantly cross-react with the antibodies, except for a few analogues. The availability of this sensitive assay makes it possible to evaluate the pharmacokinetics of SCH 40120 in man.
SCH 40120是一种正在研发的强效急性抗炎剂，用于局部治疗皮肤炎症和过敏性疾病，如特应性皮炎、接触性皮炎和牛皮癣。为了支持经皮吸收研究，开发了一种竞争性酶免疫测定法（EIA）来测定未提取血浆样品中的SCH 40120。SCH 38280是SCH 40120的羧化类似物，用作半抗原并与牛甲状腺球蛋白（Thy）偶联。半抗原-Thy偶联物用作免疫原免疫兔子以产生抗体。半抗原还与辣根过氧化物酶（HRP）偶联形成SCH 38280-HRP，用作示踪剂。该EIA可检测低至50 pg/ml血浆的SCH 40120浓度，并且能够可靠地定量血浆样品中100 pg/ml至10 ng/ml的SCH 40120，具有良好的线性、准确性和精密度。除了少数类似物外，各种结构相关的化合物和潜在代谢物与抗体没有明显的交叉反应。这种灵敏测定法的可用性使得评估SCH 40120在人体中的药代动力学成为可能。
