An improved LC–MS/MS method for determination of docetaxel and its application to population pharmacokinetic study in Chinese cancer patients |
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Authors: | Jia Yang Xingang Li Wenjun Li Xin Xi Qian Du Feng Pan Songqing Liu |
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Affiliation: | 1. Department of Pharmacy, The Third Affiliated Hospital (Gener Hospital), Chongqing Medical University, Chongqing, China;2. Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China;3. Department of Biomedical Analysis and Testing Center, Medical University of the Army Force, Chongqing, China |
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Abstract: | 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 C18 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. |
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Keywords: | docetaxel LC–MS/MS population pharmacokinetics sodium adducts |
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