Abstract
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.
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