title: 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: 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.
  
  
  
  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.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China.
authors.forename: Rui-Miao
authors.initials: RM
authors.lastname: Chang
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China.
authors.forename: Ai-Guo
authors.initials: AG
authors.lastname: Zeng
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China.
authors.forename: Xin-Ya
authors.initials: XY
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China.
authors.forename: Sai-Jie
authors.initials: SJ
authors.lastname: Zuo
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China.
authors.forename: Chun
authors.initials: C
authors.lastname: Chang
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu