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[c,g]carbazole (DBC) and made it possible to accumulate greater amounts of metabolites for comprehensive chemical structural elucidation and quantification without the use of radiolabeled DBC. High-resolution mass spectral data and 1H NMR and fluorescence spectra were used to confirm the existence 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 synthesized acetoxy-DBC derivatives as standards, the HPLC external standard method was employed for quantitation of the major DBC metabolites after acetylation. The quantities of 5-OH-DBC, 3-OH-DBC, 1-OH-DBC, and DBC in the metabolite mixture determined using the external standard method were found to agree with those calculated using the radiometric method. Acetylation is a promising nonradiometric qualitative and quantitative technique for further metabolism studies of DBC and analogues which produce unstable monohydroxylated metabolites.
Xue
W
W
Department of Environmental Health, University of Cincinnati Medical Center, Ohio 45267-0056.
Schneider
J
J
Jayasimhulu
K
K
Warshawsky
D
D
D000107:Acetylation; D000818:Animals; D002227:Carbazoles / Q000737:chemistry / Q000378:metabolism*; D002273:Carcinogens / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism*; D010636:Phenols / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002227:Carbazoles; D002273:Carcinogens; D010636:Phenols; C013478:7H-dibenzo(c,g)carbazole