In vivo metabolism of 2-[1'-phenyl-3'-(3-chlorophenyl)-2'-propenylyden]hydrazino-3-methyl-4(3H)-quinazolinone in rats.
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 dissolved in DMSO/water (1:4) and administered intraperitoneally at a dose of 100 mg/kg in a volume of approximately 0.1 mL. Blood samples were taken before and 30 min, 1.5, 3, 6, 9, 11, 30 and 48 h after i.p. drug administration. The chromatographic separation of the substrate and its metabolites was performed using a stainless steel Novopak C18 column (150 x 4.6 mm i.d., 5-microm particle size). The optimal composition of the mobile phase was reached 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 (M1) and 3-(3-chlorophenyl)-1-phenylprop-2-en-1-one (M2) derivatives were identified together with substrate by comparing them to reference standards using HPLC-UV/DAD. In addition, the composition of these metabolites and substrate was confirmed by LC-MS in plasma.
Kaymakçioğlu
Bedia Koçyiğit
BK
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, Istanbul, Turkey.
Aktan
Yasemin
Y
Süzen
Sibel
S
Gökhan
Nesrin
N
Koyunoğlu
Semra
S
Erol
Kevser
K
Yeşilada
Akgül
A
Rollas
Sevim
S
D000107:Acetylation; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D006834:Hydrazines / Q000378:metabolism* / Q000493:pharmacokinetics; D006868:Hydrolysis; D007274:Injections, Intraperitoneal; D013058:Mass Spectrometry; D011799:Quinazolines / Q000378:metabolism* / Q000493:pharmacokinetics; D052999:Quinazolinones; D051381:Rats
C508269:2-(1'-phenyl-3'-(3-chlorophenyl)-2'-propenylidene)hydrazino-3-methyl-4(3H)-quinazolinone; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006834:Hydrazines; D011799:Quinazolines; D052999:Quinazolinones