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An improved LC–MS/MS method for determination of cinacalcet in human plasma and its application to the evaluation of food intake effect on the pharmacokinetics of cinacalcet in healthy volunteers
Author(s) -
Li Linling,
Chen Caili,
Cai Ningfang,
Yi Jinling,
Zheng Chao,
Feng Yan,
Xiong Wengang,
Luo Xi,
Li Weihua,
Cheng Zeneng
Publication year - 2019
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4631
Subject(s) - cinacalcet , chemistry , pharmacokinetics , chromatography , human plasma , pharmacology , calcium , organic chemistry , parathyroid hormone , medicine , secondary hyperparathyroidism
A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the determination of cinacalcet in human plasma was developed and validated. This assay was based on liquid–liquid extraction and cinacalcet‐d4 was used as an internal standard (IS). Separation was achieved on a C 18 column by the mobile phase A of water (containing 0.1% formic acid) and the mobile phase B of acetonitrile–water (95:5, v/v) (containing 0.2% formic acid) with gradient elution. Quantification was done using multiple reaction monitoring mode to monitor the precursor‐to‐product ion transitions of m / z 358.2 → m / z 155.2 for cinacalcet and m / z 362.3 → m / z 155.0 for IS at positive ionization mode. The calibration curve was established over the range 0.05–20.0 ng/mL and the correlation coefficient was >0.99. The intra‐ and inter‐day relative standard deviations were <5.8%. Accuracy determined at four concentrations ranged between 96.0 and 106.0%. This method was successfully applied to a pharmacokinetic description of oral dose of cinacalcet and the significant effect of food intake on the pharmacokinetics of cinacalcet was first demonstrated in Chinese healthy volunteers.