Authors: Joyce S Macwan Ileana A Ionita Fatemeh Akhlaghi
Publish Date: 2011/11/23
Volume: 402, Issue: 3, Pages: 1217-1227
Abstract
A simple and sensitive assay was developed and validated for the simultaneous quantification of rosuvastatin acid RST rosuvastatin5Slactone RSTLAC and Ndesmethyl rosuvastatin DMRST in buffered human plasma using liquid chromatography–tandem mass spectrometry LCMS/MS All the three analytes and the corresponding deuteriumlabeled d6 internal standards were extracted from 50 μL of buffered human plasma by protein precipitation The analytes were chromatographically separated using a ZorbaxSB Phenyl column 21 mm × 100 mm 35 μm The mobile phase comprised of a gradient mixture of 01 v/v glacial acetic acid in 10 v/v methanol in water solvent A and 40 v/v methanol in acetonitrile solvent B The analytes were separated at baseline within 60 min using a flow rate of 035 mL/min Mass spectrometry detection was carried out in positive electrospray ionization mode The calibration curves for all three analytes were linear R ≥ 09964 n = 3 over the concentration range of 01–100 ng/mL for RST and RSTLAC and 05–100 ng/mL for DMRST Mean extraction recoveries ranged within 880–106 Intra and interrun mean percent accuracy were within 918–111 and percent imprecision was ≤15 Stability studies revealed that all the analytes were stable in matrix during benchtop 6 h on ice–water slurry at the end of three successive freeze and thaw cycles and at −80°C for 1 month The method was successfully applied in a clinical study to determine the concentrations of RST and the lactone metabolite over 12h postdose in patients who received a single dose of rosuvastatin
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