A sensitive enzyme immunoassay (EIA) for quantitation of the topical anti-inflammatory agent SCH 40120 in unextracted human plasma.
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.
Wang
C J
CJ
Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, NJ 07033.
Tian
Z
Z
Gommoll
C
C
Reyes
V
V
Lin
C C
CC
D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D006735:Horseradish Peroxidase; D006801:Humans; D007124:Immunoenzyme Techniques; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D009287:Naphthyridines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D011817:Rabbits; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013954:Thyroglobulin
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016859:Lipoxygenase Inhibitors; D009287:Naphthyridines; C076031:Sch 40120; D013954:Thyroglobulin; D006735:Horseradish Peroxidase