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An improved LC–MS/MS method for determination of docetaxel and its application to population pharmacokinetic study in Chinese cancer patients
Author(s) -
Yang Jia,
Li Xingang,
Li Wenjun,
Xi Xin,
Du Qian,
Pan Feng,
Liu Songqing
Publication year - 2020
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.4857
Subject(s) - chemistry , chromatography , protein precipitation , pharmacokinetics , analyte , docetaxel , calibration curve , selected reaction monitoring , paclitaxel , extraction (chemistry) , population , mass spectrometry , triple quadrupole mass spectrometer , detection limit , tandem mass spectrometry , pharmacology , cancer , medicine , demography , sociology
Because of its unpredictable side effects and efficacy, the anticancer drug docetaxel (DTX) requires improved characterisation of its pharmacokinetic profiles through population pharmacokinetic studies. A sensitive and rugged LC–MS/MS method for the detection of DTX in human plasma was developed and optimised using paclitaxel as an internal standard (IS). The plasma samples underwent rapid extraction using hybrid solid‐phase extraction‐protein precipitation. The analyte and IS were separated with an isocratic system on a Zorbax Eclipse Plus C 18 column using water containing 0.05% acetic acid along with 20 μM of sodium acetate and methanol (30/70, v/v) as the mobile phase. Quantification was performed using a triple quadrupole mass spectrometer through multiple reaction monitoring in positive mode, using the m / z 830.3 → 548.8 and m / z 876.3 → 307.7 transitions for DTX and paclitaxel, respectively. The range of the calibration curve was 1–500 ng/mL for DTX, and the linear correlation coefficient was >0.99. The accuracies ranged from −4.6 to 4.2%, and the precision was no higher than 7.0% for the analytes. No significant matrix effect was observed. Both DTX and the IS showed considerable recovery. This method was finally applied to the establishment of a population pharmacokinetic model to optimise the clinical use of DTX.