Validated liquid chromatography-tandem mass spectrometry method for quantification of ticagrelor and its active metabolite in human plasma

A rapid, simple and sensitive LC-MS/MS method was established and validated for simultaneous quantification of ticagrelor and its active metabolite AR-C124910XX in human plasma. After plasma samples were deproteinized with acetonitrile, the post-treatment samples were chromatographed on a Dikma C-18 column interfaced with a triple quadrupole tandem mass spectrometer. Electrospray negative ionization mode and multiple reaction monitoring were adopted to assay ticagrelor and AR-C124910XX. Acetonitrile and 5 mM ammonium acetate was used as the mobile phase with a gradient elution at a flow rate of 0.5 mL/min. The method was linear in the range of 0.781-800 ng/mL for both ticagrelor and AR-C124910XX with a correlation coefficient >= 0.994. The intra- and inter-day precisions were within 12.61% in terms of relative standard deviation and the accuracy was within +/- 7.88% in terms of relative error. The LC-MS/MS method was fully validated for its sensitivity, selectivity, stability, matrix effect and recovery. This convenient and specific LC-MS/MS method was successfully applied to the pharmacokinetic study of ticagrelor and AR-C124910XX in healthy volunteers after an oral dose of 90 mg ticagrelor.