Simultaneous determination of donafenib and its N-oxide metabolite in human plasma by liquid chromatography-tandem mass spectrometry
10.16438/j.0513-4870.2016-0954
- VernacularTitle:LC-MS/MS法同时测定人血浆中多纳非尼及其N-氧化代谢物
- Author:
Jing WANG
1
;
Bin-hua LÜ
2
;
Xiao-jian DAI
3
;
Yi-fan ZHANG
3
;
Xiao-yan CHEN
3
;
Da-fang ZHONG
1
Author Information
1. College of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, China
2. Suzhou Zelgen Biopharmaceuticals Co., Ltd., Kunshan 215300, China
3. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
LC-MS/MS;
donafenib;
sorafenib;
N-oxide metabolite
- From:
Acta Pharmaceutica Sinica
2017;52(3):443-448
- CountryChina
- Language:Chinese
-
Abstract:
Donafenib is the deuterium derivative of sorafenib, and is an anti-tumor drug in clinical trials. An accurate and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of donafenib and its N-oxide metabolite in human plasma. The analytes and internal standards (sorafenib and sorafenib N-oxide) were extracted from plasma by protein precipitation with acetonitrile, and separated on a Gemini C18 (50 mm×2.0 mm, 5 μm) column using a gradient elution procedure. The mobile phase consisted of acetonitrile and 5 mmol·L-1 ammonium acetate (0.2% formic acid) at a flow rate of 0.7 mL·min-1. The total run time was 5.0 min. Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 468.2→273.2 for donafenib and m/z 465.2→270.2 for its internal standard sorafenib, m/z 484.2→289.2 for donafenib N-oxide and m/z 481.2→286.2 for its internal standard sorafenib N-oxide. The standard curves were linear in the range of 5.00-5 000 ng·mL-1 for donafenib, and 1.00-1 000 ng·mL-1 for donafenib N-oxide. The method was validated and successfully applied to the pharmacokinetics study of donafenib tosylate tablets in volunteers.
