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Journal of Chinese Pharmaceutical Sciences ›› 2017, Vol. 26 ›› Issue (1): 45-52.DOI: 10.5246/jcps.2017.01.004

• Original articles • Previous Articles     Next Articles

Determination of mefunidone, a novel anti-fibrotic agent analogue of pirfenidone, in plasma by HPLC-UV and its pharmacokinetic application in rats

Zhou Wen1, Shan Ji1, Feifan Xie2, Gaoyun Hu1, Zeneng Cheng1*   

  1. 1. School of Pharmaceutical Sciences, Central South University, Changsha 410013, China
    2. Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Science, Ghent University, Ghent B-9000, Belgium
  • Received:2016-09-15 Revised:2016-10-27 Online:2017-01-22 Published:2016-11-15
  • Contact: Tel.: +86-731-82650451, E-mail: chengzn@csu.edu.cn
  • Supported by:
    National Natural Science Foundation of China (Grant No. 81573498), and supported by Nanxin Pharmaceutical Co., Ltd. (Guangdong, China).

Abstract:

Mefunidone (MFD), a pirfenidone analogue, has been suggested as a novel anti-fibrotic agent in preclinical research stage. In this work, we developed a sensitive and specified HPLC-UV method and validated it for the determination of MFD in rat plasma. A cost-effective protein precipitation method using methanol was used to process the plasma samples, and pirfenidone was employed as the internal standard (IS). Chromatographic separation was performed on an Agilent ZORBAX SB-Aq column (4.6 mm×250 mm, 5 μm) with a mobile phase consisting of 10 mM ammonium formate solution (pH 3.0, adjusted by 1.5‰ formic acid)–acetonitrile–methanol (60:23:17, v/v/v) at a flow rate of 1.0 mL/min, and the samples were monitored at an ultraviolet wavelength of 245 nm. The retention times of MFD and IS were 5.5 and 7.8 min, respectively. The calibration curve was linear (r2 = 0.9997) between 0.1 and 20 μg/mL. The intra- and inter-day precisions were within 8.6%, and the bias of intra- and inter-accuracies of the method was between –4.2% and 6.5%. The method was successfully applied to pharmacokinetic study of MFD after i.g. and i.v. administration in rats. The elimination half-life was (3.41±0.81) h for i.g. administration and (2.26±0.87) h for i.v. administration. The absolute bioavailability of MFD in rat was 79.1%.  

Key words: Mefunidone, Anti-fibrotic, HPLC-UV, Pharmacokinetics, Bioavailability

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