SYNTHESIS AND MASS-SPECTROMETRIC CHARACTERIZATION OF HUMAN SERUM ALBUMINS MODIFIED BY COVALENT BINDING OF 2 NONSTEROIDAL ANTIINFLAMMATORY DRUGS - TOLMETIN AND ZOMEPIRAC

Human serum albumins modified by covalently bound tolmetin or zomepira c were synthesized as models for similar products formed in vivo from acyl glucuronides. Activated esters of both drugs were prepared with 1 -ethyl-3-(3-dimethylaminopropyl)-carbodi-imide, and then allowed to re act with human serum albumin. Tryptic digests of both protein products were analysed by HPLC to identify peptides containing covalently boun d drugs, and binding sites on albumin were identified by highperforman ce tandem MS. Three binding sites were common to both products, i.e. l ysine-195, -199 and -351. Three further modified residues were identif ied for the tolmetin-albumin product, i.e. aspartic acid 1, and lysine -524 and -536.