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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
Author(s) -
Yuan Yin,
Zhou Xuan,
Li Jian,
Ye Suofu,
Ji Xiwei,
Li Liang,
Zhou Tianyan,
Lu Wei
Publication year - 2015
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.3316
Subject(s) - chemistry , chromatography , pharmacokinetics , dexamethasone , plasma , pharmacology , medicine , physics , quantum mechanics
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 C 18 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.