Xue W, Schneider J, Jayasimhulu K, Warshawsky D
Department of Environmental Health, University of Cincinnati Medical Center, Ohio 45267-0056.
Chem Res Toxicol. 1993 May-Jun;6(3):345-50. doi: 10.1021/tx00033a015.
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.
乙酰化作用使7H-二苯并[c,g]咔唑（DBC）的酚类代谢产物得以稳定，从而能够在不使用放射性标记DBC的情况下积累更多代谢产物，用于全面的化学结构解析和定量分析。利用高分辨率质谱数据、1H核磁共振谱和荧光光谱，证实了在3-甲基胆蒽诱导的大鼠肝微粒体体外形成的乙酰化代谢产物混合物中存在5-羟基-DBC、3-羟基-DBC、1-羟基-DBC以及氧化二聚体6,6'-双-(5-羟基-DBC)。以合成的乙酰氧基-DBC衍生物作为标准品，采用高效液相色谱外标法对乙酰化后的主要DBC代谢产物进行定量分析。结果发现，使用外标法测定的代谢产物混合物中5-羟基-DBC、3-羟基-DBC、1-羟基-DBC和DBC的含量与采用放射性方法计算得到的结果一致。对于DBC及其产生不稳定单羟基化代谢产物的类似物，乙酰化是一种有前景的非放射性定性和定量技术，可用于进一步的代谢研究。
