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.

Semi-Mechanism-Based Pharmacokinetic/Pharmacodynamic Model for the Combination Use of Dexamethasone and Gemcitabine in Breast Cancer

“…The PK profiles in combination model were also derived from the simulation based on the PK parameters obtained from previous study and literature . To the best of our knowledge, although there has been no report aiming at the PK interaction between DEX and GM in BALB/c female nude mice, Leggas et al have investigated the PK interaction between the two drugs in human and no significant difference was observed in PK parameters.…”

“…The PK of DEX was characterized by a two‐compartment model with first‐order absorption, whereas the PK of GM was characterized by a two‐compartment model without absorption compartment since GM was administered via intravenous (i.v.) injection .…”

“…injection . The PK parameters of DEX were obtained from our former study, and the PK parameters of GM were obtained from literature …”

Time-dependent pharmacokinetics of dexamethasone and its efficacy in human breast cancer xenograft mice: a semi-mechanism-based pharmacokinetic/pharmacodynamic model

“…The plasma concentrations of DEX after single or multiple doses in nude mice were determined by the LC-MS/MS method that was previously published by our group [15] . The range of the calibration curve was 2.5-500 ng/mL, and the selectivity, linearity, precision, accuracy, recovery, stability, matrix effect and dilution effect of the method were eligible.…”

LC–MS/MS method for simultaneous determination of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin in serum of multiple myeloma patients

“…However, to date, no bioanalytical LC-MS/MS method has been reported for simultaneous quantification of the above drugs that were commonly used in MM chemotherapy. The present assay methods only contained one or two of these drugs had been published [14][15][16][17][18][19][20][21][22][23][24] and the representative comparison result was shown in Table 1. Shanghai Eastern Hepatobiliary Hospital was a research center specialized in hematology and oncology notably for myeloma and lymphoma.…”