Development and validation of an HPLC assay for the quantitation of mefunidone, a novel derivative of pirfenidone, and an initial pharmacokinetics study in liver microsomes

doi:10.5246/jcps.2018.03.020

Journal of Chinese Pharmaceutical Sciences ›› 2018, Vol. 27 ›› Issue (3): 193-200.DOI: 10.5246/jcps.2018.03.020

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Development and validation of an HPLC assay for the quantitation of mefunidone, a novel derivative of pirfenidone, and an initial pharmacokinetics study in liver microsomes

Yanfen Chen^2#, Meng Sun^1#, Shixi Zhang³, Zeneng Cheng^1*, Gaoyun Hu¹, Qubo Zhu^1*

1. The School of Pharmaceutical Sciences in Central South University, Changsha 410013, Hunan, China
2. Department of Pharmacy, Zhongshan Hospital Xiamen University, Xiamen, Fujian 361004, China
3. The Guangzhou South Xin Pharmaceutical Co, Guangzhou 510630, Guangdong, China

Received:2017-12-10 Revised:2018-01-15 Online:2018-03-31 Published:2018-02-27
Contact: Tel.: +86-731-82650451, Fax: +86-731-82650446, E-mail: chengzn@csu.edu.cn; biqbz@hotmail.com
Supported by:
The National Natural Science Foundation of China (Grant No. 81302819), the National Natural Science Foundation of China (Grant No. C0709-31201056), the Fundamental Research Funds for the Central Universities of China (Grant No. 7601110179) and the Fundamental Research Funds for the Central south Universities of China (Grant No. 2016zzts494).

Abstract

Abstract:

本研究开发了一种简单可靠的HPLC-UV方法用于美氟尼酮的测定。生物分析步骤包括从500 μL肝微粒体系统中通过甲醇沉淀蛋白质提取美氟尼酮。色谱条件:色谱柱为Agilent TC-C₁₈柱(4.6 mm×250 mm, 5 μm), 流动相为10 mM甲酸铵(用10%的甲酸调PH至2.9)–乙腈(70:30, v/v),流速为1.0 mL/min, UV检测波长设定在245 nm。美氟尼酮和吡非尼酮(内标物)分别在6.0和9.7分钟洗脱,总运行时间为12分钟。根据美国食品和药物管理局生物分析指南,进行了方法验证,结果符合验收标准。美氟尼酮在肝微粒体中的标准曲线在0.5–16 μg/mL范围内呈线性关系。美氟尼酮内和外间精确度低于9.0％,偏差在±10.0％以内。美氟尼酮在肝微粒体中孵育后,该方法成功应用于药代动力学研究。

Key words: 美氟尼酮, HPLC分析, 药代动力学, 肝微粒体, 衍生物

CLC Number:

R969.1

Supporting:

Yanfen Chen, Meng Sun, Shixi Zhang, Zeneng Cheng, Gaoyun Hu, Qubo Zhu. Development and validation of an HPLC assay for the quantitation of mefunidone, a novel derivative of pirfenidone, and an initial pharmacokinetics study in liver microsomes[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(3): 193-200.

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Development and validation of an HPLC assay for the quantitation of mefunidone, a novel derivative of pirfenidone, and an initial pharmacokinetics study in liver microsomes

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