Development and validation of a highly sensitive LC‐MS/MS method for the determination of dexamethasone in nude mice plasma and its application to a pharmacokinetic study |
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Authors: | Yin Yuan Xuan Zhou Jian Li Suofu Ye Xiwei Ji Liang Li Tianyan Zhou Wei Lu |
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Affiliation: | 1. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China;2. School of Pharmaceutical science, Peking University, Beijing, China |
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Abstract: | In the current study, a simple, sensitive and rapid analytical method for the determination of dexamethasone was developed and applied to a pharmacokinetic study in nude mice. Using testosterone as an internal standard, a liquid chromatography–tandem mass spectrometry (LC‐MS/MS) approach after one‐step precipitation with acetonitrile was validated and used to determine the concentrations of dexamethasone in nude mice plasma. The method utilized a simple isocratic reverse phase separation over a Dionex C18 column with a mobile phase composed of acetonitrile–water (40:60, v/v). The analyte was detected by a triple quadrupole tandem mass spectrometer via electrospray and multiple reaction monitoring was employed to select both dexamethasone at m/z 393.0/147.1 and testosterone at m/z 289.5/97.3 in the positive ion mode. The calibration curves were linear (r >0.99) ranging from 2.5 to 500 ng/mL with a lower limit of quantitation of 2.5 ng/mL. The relative standard deviation ranged from 1.69 to 9.22% while the relative error ranged from ?1.92 to ?8.46%. This method was successfully applied to a preclinical pharmacokinetic study of dexamethasone and its pharmacokinetics was characterized by a two‐compartment model with first‐order absorption in female nude mice. Copyright © 2014 John Wiley & Sons, Ltd. |
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Keywords: | LC‐MS/MS dexamethasone nude mice pharmacokinetics |
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