title: 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.
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.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Yuan
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Suofu
authors.initials: S
authors.lastname: Ye
authors.forename: Xiwei
authors.initials: X
authors.lastname: Ji
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Tianyan
authors.initials: T
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003907:Dexamethasone / Q000097:blood* / Q000493:pharmacokinetics; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D003907:Dexamethasone
keywords: LC-MS/MS; dexamethasone; nude mice; pharmacokinetics