Lang D, Criegee D, Grothusen A, Saalfrank R W, Böcker R H
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Germany.
Drug Metab Dispos. 1996 Aug;24(8):859-65.
The in vitro metabolism of four s-triazine herbicides (atrazine, terbuthylazine, ametryne, and terbutryne) was studied using liver microsomes from rats, pigs, and humans. New HPLC methods with UV detection were developed for the analyses of the incubations. Principal phase I reactions were N-monodealkylation, hydroxylation of the isopropyl or tert-butyl moiety, and sulfoxidation of the substrates in all species. Bidealkylation, 2-hydroxylation, or cleavage of the tert-butyl moiety could not be found in this system. The sulfoxidation of the 2-methylthio-s-triazines exceeded catalysis of the other metabolic reactions by 3-4-fold in all species. In general, all species produced the same types of metabolites, but with species-specific differences in the ratios of the metabolites. Species-specific stereoselective formation of a new chiral isopropyl-hydroxylated metabolite from atrazine was investigated using chiral HPLC techniques. The stereoselective production of this metabolite was different in the different species, with S/R ratios of 76:24 in rats, 49:51 in pigs, and 28:72 in humans.
使用大鼠、猪和人类的肝微粒体研究了四种均三嗪类除草剂（莠去津、特丁津、莠灭净和特丁净）的体外代谢。开发了带有紫外检测的新型高效液相色谱法用于分析孵育物。所有物种的主要Ⅰ相反应均为N-单脱烷基化、异丙基或叔丁基部分的羟基化以及底物的亚砜化。在该系统中未发现双脱烷基化、2-羟基化或叔丁基部分的裂解。在所有物种中，2-甲硫基均三嗪的亚砜化比其他代谢反应的催化作用高3至4倍。一般来说，所有物种产生的代谢物类型相同，但代谢物比例存在物种特异性差异。使用手性高效液相色谱技术研究了从莠去津立体选择性形成一种新的手性异丙基羟基化代谢物的物种特异性。这种代谢物的立体选择性产生在不同物种中有所不同，大鼠中的S/R比为76:24，猪中的为49:51，人类中的为28:72。
