PT  - JOURNAL ARTICLE
AU  - R B van Breemen
AU  - C C Fenselau
TI  - Reaction of 1-O-acyl glucuronides with 4-(p-nitrobenzyl)pyridine.
DP  - 1986 Mar 01
TA  - Drug Metabolism and Disposition
PG  - 197--201
VI  - 14
IP  - 2
4099  - http://dmd.aspetjournals.org/content/14/2/197.short
4100  - http://dmd.aspetjournals.org/content/14/2/197.full
SO  - Drug Metab Dispos1986 Mar 01; 14
AB  - In this investigation, 31 1-O-acyl glucuronides were synthesized and 25 of these were shown to react with 4-(p-nitrobenzyl)pyridine (NBP), a standard chemical nucleophil, on thin layer chromatography plates. A quantitative NBP assay was developed based on existing methods, and the rates of reaction of three acyl glucuronides, clofibric 1-O-acyl glucuronide, indomethacin 1-O-acyl glucuronide, and flufenamic 1-O-acyl glucuronide, were determined. These rates ranged from 0.436 min-1 to 1.08 min-1. Chlorambucil, a powerful alkylating agent, reacted with NBP 127 times faster than the most reactive of the three glucuronides assayed. The half-lives of these three 1-O-acyl glucuronides, determined at pH 2.0, 4.0, 6.0, 7.4, and 10.0 in aqueous phosphate solution, ranged from greater than 1000 hr at pH 2 to less than 1 min at pH 10.0. Determination of the rates of reaction of 1-O-acyl glucuronides with NBP and the rates of hydrolysis as a function of pH further characterize these compounds as activated phase II metabolites.