title: Development and validation of a sensitive LC-MS/MS assay for simultaneous quantitation of ranolazine and its three metabolites in human plasma.
abstract: A rapid, sensitive and reliable LC-MS/MS method was developed and validated for the simultaneous determination of ranolazine and its three metabolites, CVT-2514, CVT-2738, and CVT-4786, in human plasma. The plasma samples were prepared by protein precipitation. Chromatographic separation was achieved on a Gemini C(18) column (50 mm × 2.0 mm, 5 μm) using methanol: 5 mM ammonium acetate as the mobile phase with gradient elution. Mass detection was carried out by electrospray ionization in both positive and negative ion multiple reaction monitoring (MRM) modes. The calibration curves were linear over a concentration range of 4-2000 ng/mL for ranolazine, 4-1000 ng/mL for CVT-2514 and CVT-2738 and 8-1000 ng/mL for CVT-4786. The intra-day and inter-day accuracy and precision were within the acceptable limits of ±15% at all concentrations. The method was successfully applied for the simultaneous estimation of ranolazine and its three metabolites in human plasma from a clinical pharmacokinetics study.
authors.affiliation: School of Pharmacy, Yantai University, Yantai, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
authors.forename: Zuoming
authors.initials: Z
authors.lastname: Sun
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wanhui
authors.initials: W
authors.lastname: Liu
authors.forename: Dafang
authors.initials: D
authors.lastname: Zhong
mesh_terms: D000083:Acetanilides / Q000097:blood*; D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000097:blood; D006801:Humans; D016014:Linear Models; D010879:Piperazines / Q000097:blood*; D000069458:Ranolazine; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000083:Acetanilides; D004791:Enzyme Inhibitors; D010879:Piperazines; D000069458:Ranolazine