An HPLC method for the determination of a novel anti-hypertension agent 6,7-dimethoxy-3-(4-(4-fluorobenzyloxy)-3-methoxyphenylmethyl)quinazolin-4(3H)-one in rat plasma: application to pharmacokinetic study.

Abstract

UNLABELLED:

6,7-dimethoxy-3-(4-(4-fluorobenzyloxy)-3-methoxyphenylmethyl) quinazolin-4(3H)-one (DFMQ-19), a novel analogue of 3-benzylquinazolin-4(3H)-ones, may be considered as a drug candidate for the treatment of hypertension. The aim of this study was to develop and validate a reverse-phase high-performance liquid chromatography to determine the DFMQ-19 in plasma and demonstrate its application in pharmacokinetic study. Separation of DFMQ-19 and I.S (structural analog of DFMQ-19) was performed using Shim-Pack VP-ODS column and a mixture of acetonitrile and water as mobile phase. The HPLC method was validated according to the ICH guidelines. The limit of detection and lower limit of quantitation were 0.05 µg/ml and 0.1 µg/ml respectively. The recovery rate of DFMQ-19 from blood samples was >81% of the spiked amount. The RSD of the intra- and inter-day precisions was within 7.5%, and RE of accuracy was between -14.4% and 4.5%. This method was successfully applied to the pharmacokinetic study after administration of DFMQ-19. The pharmacokinetic parameters, such as half-life (t1/2 ), mean residence time (MRT), maximum concentration (Cmax ) were determined. Based on these pharmacokinetic parameters, the oral bioavailability of DFMQ-19 was calculated to be 13.42% in rat. This article is protected by copyright. All rights reserved.

HIGHLIGHTS:

HPLC method was validated to quantify DFMQ-19 in rat plasma I.S is one of the structural analogs of the analyte The HPLC method was validated according to the ICH guidelines The oral bioavailability of DFMQ-19 was 13.42% in rat.

• Authors: Rui-Miao Chang, Ai-Guo Zeng, Wei Du, Xin-Ya Xu, Sai-Jie Zuo, Chun Chang, Qiang Fu
• Journal: Biomedical chromatography : BMC (Biomed Chromatogr) Vol. 30 Issue 7 Pg. 1118-1123 (Jul 2016) ISSN: 1099-0801 [Electronic] England
• PMID: 26579998 (Publication Type: Journal Article)
• Copyright: This article is protected by copyright. All rights reserved.