In vivo metabolism of2-[1'-phenyl-3'-(3chlorophenyl)-2'-propenylyden]hydrazino-3-methyl4(3H)-quinazolinone in rats

Abstract

The aim of this study was to investigate by HPLC the in vivo metabolism of 2-[1'-phenyl-3'-(3-chlorophenyl)-2'propenylyden]hydrazino-3-methyl-4(3H)-quinazolinone as a substrate, and as a model compound in rats. The substrate was dissolvedin DMSO/water (1:4) and administered intraperitoneally at a dose of 100mg/kgin a volume of approximately 0.1 mL. Blood samples were taken before and 30 min, 1.5,3,6,9, 11,30and 48 h after i.p, drug administration. The chromatographic separation of the substrate and its metabolites was performed usinga stainless steel Novopak CI8 column (150 x 4.6 mm i.d.,5urnparticle size).The optimal composition of the mobile phase wasreached by introducing different mixtures of pure acetonitrile and water in a linear gradient system. Following the biotransformation of this compound, 2-hydrazino-3-methyl-4(3H)quinazolinone (MI) and 3-(3-chlorophenyl)-I-phenylprop-2-en-l-one (M2) derivatives were identified together withsubstrate by comparing them to reference standards usingHPLC-UV/DAD.In addition, the composition of these metabolites andsubstrate was confirmed by LC-MS in plasma