Rapid and simultaneous determination of nifedipine and dehydronifedipine in human plasma
10.16438/j.0513-4870.2018-0764
- VernacularTitle:LC-MS/MS法测定人血浆中硝苯地平和去氢硝苯地平
- Author:
Xue-fei CHEN
1
;
Xiang-yu HOU
2
;
Xiao-yan CHEN
2
;
Da-fang ZHONG
1
Author Information
1. College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Publication Type:Research Article
- Keywords:
LC-MS/MS;
nifedipine;
ehydronifedipine
- From:
Acta Pharmaceutica Sinica
2019;54(2):360-365
- CountryChina
- Language:Chinese
-
Abstract:
Nifedipine, a calcium channel antagonist, is metabolized mainly by CYP3A4 to dehydronifedipine. A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously determine nifedipine and dehydronifedipine in human plasma using d6-nifedipine/d6-dehydronifedipine as internal standards. After extraction from the plasma by protein precipitation, the analytes and internal standard were separated on a Hypersil Gold C18 (50 mm×2.1 mm, 1.9 μm). The mobile phase consisted of methanol and 5 mmol·L-1ammonium acetate aqueous solution (0.1% formic acid). Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 347.3→254.1 for nifedipine, m/z 345.2→283.9 for dehydronifedipine, m/z 353.3→257.1 for d6-nifedipine, m/z 351.2→286.9 for d6-dehydronifedipine. The method had a linear calibration curves over the concentrations of 0.10-80.0 ng·mL-1 for nifedipine and 0.050-40.0 ng·mL-1 for dehydronifedipine. The validated LC-MS/MS method has been successfully used study pharmacokinetic interactions of apatinib (CYP3A4 inhibitor) and nifedipine (CYP3A4 substrate) in human. This clinical trial was approved by the society of ethics and conducted in the first hospital of China medical university.
