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

作者：Chang, Rui-Miao; Zeng, Ai-Guo; Du, Wei; Xu, Xin-Ya; Zuo, Sai-Jie; Chang, Chun; Fu, Qiang^*

来源：Biomedical Chromatography, 2016, 30(7): 1118-1123.

DOI：10.1002/bmc.3659

• high-performance liquid chromatography
• pharmacokinetic
• bioavailability
• anti-hypertension
• DFMQ-19

6,7-Dimethoxy-3-[4-(4-fluorobenzyloxy)-3-methoxyphenylmethyl] quinazolin-4(3H)-one (DFMQ-19), a novel analog 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 studies. Separation of DFMQ-19 and IS (structural analog of DFMQ-19) was performed using a Shim-Pack VP-ODS column and a mixture of acetonitrile and water as mobile phase. The HPLC method was validated according to the International Conference on Harmonization guidelines. The limit of detection and lower limit of quantitation were 0.05 and 0.1 g/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, mean residence time and maximum concentration were determined. Based on these pharmacokinetic parameters, the oral bioavailability of DFMQ-19 was calculated to be 13.42% in rat.

• 出版日期2016-7
• 单位西安交通大学