PT  - JOURNAL ARTICLE
AU  - D D Shoemaker
AU  - R L Cysyk
AU  - S Padmanabhan
AU  - H B Bhat
AU  - L Malspeis
TI  - Identification of the principal biliary metabolite of 4'-(9-acridinylamino)methanesulfon-m-anisidide in rats.
DP  - 1982 Jan 01
TA  - Drug Metabolism and Disposition
PG  - 35--39
VI  - 10
IP  - 1
4099  - http://dmd.aspetjournals.org/content/10/1/35.short
4100  - http://dmd.aspetjournals.org/content/10/1/35.full
SO  - Drug Metab Dispos1982 Jan 01; 10
AB  - 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.