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二乙基亚硝胺和N-亚硝基吡咯烷生成的烷基化中间体的半衰期:一种测量代谢产生的活性物质的方法。

The half-lives of alkylating intermediates from diethylnitrosamine and N-nitrosopyrrolidine: a method for the measurement of metabolically generated reactive species.

作者信息

Keenan T H, Weinkam R J

出版信息

Toxicol Appl Pharmacol. 1985 Apr;78(2):316-20. doi: 10.1016/0041-008x(85)90295-9.

Abstract

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.

摘要

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。

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