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Simultaneous determination of donafenib and its N-oxide metabolite in human plasma by liquid chromatography-tandem mass spectrometry
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Jing WANG1, 2, Bin-hua LÜ3, Xiao-jian DAI2, Yi-fan ZHANG2, Xiao-yan CHEN2, Da-fang ZHONG1, 2, *
Acta Pharmaceutica Sinica | 2017, 52(3) : 443 - 448
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Acta Pharmaceutica Sinica | 2017, 52(3): 443-448
Simultaneous determination of donafenib and its N-oxide metabolite in human plasma by liquid chromatography-tandem mass spectrometry
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Jing WANG1, 2, Bin-hua LÜ3, Xiao-jian DAI2, Yi-fan ZHANG2, Xiao-yan CHEN2, Da-fang ZHONG1, 2, *
Affiliations
  • 1. College of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, China
  • 2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
  • 3. Suzhou Zelgen Biopharmaceuticals Co., Ltd., Kunshan 215300, China
Published: 2017-03-12 doi: 10.16438/j.0513-4870.2016-0954
Outline
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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.

LC-MS/MS  /  donafenib  /  sorafenib  /  N-oxide metabolite
Jing WANG, Bin-hua LÜ, Xiao-jian DAI, Yi-fan ZHANG, Xiao-yan CHEN, Da-fang ZHONG. Simultaneous determination of donafenib and its N-oxide metabolite in human plasma by liquid chromatography-tandem mass spectrometry[J]. Acta Pharmaceutica Sinica, 2017 , 52 (3) : 443 -448 . DOI: 10.16438/j.0513-4870.2016-0954
Year 2017 volume 52 Issue 3
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Article Info
doi: 10.16438/j.0513-4870.2016-0954
  • Receive Date:2016-09-28
  • Online Date:2026-01-14
  • Published:2017-03-12
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History
  • Received:2016-09-28
  • Revised:2016-10-26
Funding
Affiliations
    1. College of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, China
    2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
    3. Suzhou Zelgen Biopharmaceuticals Co., Ltd., Kunshan 215300, China
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表12种不同金属材料的力学参数

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Number of
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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