Radioimmunoassay for terfenadine in human plasma

✍ Scribed by C. E. Cook; David L. Williams; Mary Myers; C. Ray Tallent; G. A. Leeson; R. A. Okerholm; G. J. Wright

• Publisher: John Wiley and Sons
• Year: 1980
• Tongue: English
• Weight: 641 KB
• Volume: 69
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600691218

✦ Synopsis

A radioimmunoassay procedure was developed for the antihistamine terfenadine (alpha[4-(1,2-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1-piperidinebutanol). The keto analog of terfenadine was converted to its O-carboxymethyloxime derivative, which was conjugated to bovine thyroglobulin by a mixed anhydride technique. Rabbits were immunized with the resulting conjugate, and antiserums capable of binding radiolabeled terfenadine were obtained. Tritium-labeled terfenadine was prepared by a combination of exchange and reduction with platinum oxide in the presence of tritium gas, and the procedure yielded a specific activity of 48 Ci/mmole. Plasma containing terfenadine was diluted with sodium carbonate solution and extracted with hexane, and the hexane extracts were evaporated and analyzed. The between-assay coefficient of variation on control samples ranged from 8% at 10 ng/ml to 14% at 1 ng/ml. The lower practical sensitivity limit was at least as low as 0.25 ng/ml (25 pg measured). Two metabolites of terfenadine cross-reacted 16-30% with the antiserum used. However, extraction eliminated essentially all of these compounds. Analysis of plasma samples from human subjects given terfenadine showed marked intersubject variability and low plasma levels.