ACETYLATION OF PHENOLIC DERIVATIVES OF 7H-DIBENZO[C,G]CARBAZOLE - IDENTIFICATION AND QUANTITATION OF MAJOR METABOLITES BY RAT-LIVER MICROSOMES

Acetylation stabilized the phenolic metabolites of 7H-dibenzo[cg]carba zole (DBC) and made impossible to accumulate greater amounts of metabo lites for comprehensive chemical structural elucidation and quantifica tion without the use of radiolabeled DBC. High-resolution mass spectra l data and H-1 NMR and fluorescence spectra were used to confirm the e xistence of 5-OH-DBC, 3-OH-DBC, 1-OH-DBC, and the oxidative dimer, 6,6 '-bis-(5-OH-DBC), in the acetylated metabolite mixture formed in vitro by 3-methylcholanthrene-induced rat liver microsomes. Using the synth esized acetoxy-DBC derivatives as standards, the HPLC external standar d method was employed for quantitation of the major DBC metabolites af ter acetylation. The quantities of 5-OH-DBC, 3-OH-DBC, 1-OH-DBC, and D BC in the metabolite mixture determined using the external standard me thod were found to agree with those calculated using the radiometric m ethod. Acetylation is a promising nonradiometric qualitative and quant itative technique for further metabolism studies of DBC and analogues which produce unstable monohydroxylated metabolites.