Keenan T H, Weinkam R J
Toxicol Appl Pharmacol. 1985 Apr;78(2):316-20. doi: 10.1016/0041-008x(85)90295-9.
The half-times of the alpha-hydroxylated intermediates formed during metabolism of diethylnitrosamine and N-nitrosopyrrolidine have been determined. The method for determining half-times involved in vitro enzymatic conversion of the nitrosamine to a hydroxylated intermediate followed by trapping of the alkylating species generated from the chemical decomposition of the intermediate as it flowed through a column containing bound nucleophile. Half-times of less than 1 min at pH 7.4, 37 degrees C, were calculated from the distribution of alkylation on the column and the known flow rate of metabolic intermediates through the column. The half-times may be short enough to significantly limit organ distribution.
已测定二乙基亚硝胺和N-亚硝基吡咯烷代谢过程中形成的α-羟基化中间体的半衰期。测定半衰期的方法包括:首先在体外将亚硝胺酶促转化为羟基化中间体,然后当中间体流经装有结合亲核试剂的柱子时,捕获由中间体化学分解产生的烷基化物质。根据柱上烷基化的分布以及代谢中间体通过柱子的已知流速,计算出在pH 7.4、37℃条件下半衰期小于1分钟。这些半衰期可能短到足以显著限制器官分布。