TY - JOUR T1 - Identification of the principal biliary metabolite of 4'-(9-acridinylamino)methanesulfon-m-anisidide in rats. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 35 LP - 39 VL - 10 IS - 1 AU - D D Shoemaker AU - R L Cysyk AU - S Padmanabhan AU - H B Bhat AU - L Malspeis Y1 - 1982/01/01 UR - http://dmd.aspetjournals.org/content/10/1/35.abstract N2 - m-AMSA [4'-(9-acridinylamino)methanesulfon-m-anisidide] labeled in either the acridine or anilino portion was used to investigate the disposition of this antitumor agent in rats. The principal biliary metabolite, which accounts for approximately 80% of the total biliary radioactivity for 90 min after administration and greater than 50% of the administered dose by 180 min after administration, had both the acridine and the anilino portions intact. Isolation and purification of the principal metabolite was achieved by preparative thin-layer chromatography on silica gel and column chromatography on Amberlite XAD-2 resin. A nuclear magnetic resonance (NMR) spectrum of the CID salt in D2O showed that the metabolite is the m-AMSA-glutathione conjugate in which the thioether linkage occurs at the 5'-position of the anilino ring. Synthesis of the metabolite was achieved by oxidizing m-AMSA with active MnO2 to -methanesulfonyl - - (9-acridinyl)-3'-methoxy - 2',5' - cyclohexadiene-1',4'-diimine (m-AQDI) followed by reaction of m-AQDI with glutathione. The 1H-NMR spectrum of the synthetic product proved identical with that of the isolated metabolite. The demonstration that the principal biliary metabolite on m-AMSA involves glutathione bound to the 9-anilino ring suggests that m-AMSA may be bioactivated in vivo to the quinoidal diimine, m-AQDI. ER -