Lc-Ms/Ms Method for Simultaneous Determination of Decitabine and Cedazuridine in Human Plasma

Abstract

A highly sensitive, accurate, and robust LC-MS/MS method was developed and validated to simultaneously determine decitabine and cedazuridine in human plasma using azacitidine as an internal standard (IS). The analyte and IS were extracted from plasma by precipitating protein with acetonitrile and were chromatographed. The mobile phase was acetonitrile and 0.1% formic acid (75:25 v/v). Multiple reaction monitoring (MRM) mode was used, in which the transitions of 229 to m/z of 114 as MH+ion for Decitabine, m/z of 269 to m/z of 118 as MH+ion for Cedazuridine, and m/z 245.10→ 153.04 for IS were monitored. The linearity ranges from 0.15 − 250.0 ng/mL. The lower limits of quantification (LLOQ) were found to be 0.05 ng/mL for decitabine and 1.0 ng/mL for cedazuridine in human plasma. Recoveries of Decitabine ranged between 85.33% − 95.25%, and Cedazuridine ranged between 75.33% − 95.54%. The quality control sample accuracy and precision (intra-day and inter-day) were 1.25% to 1.68% and 3.01% to 6.44% for Decitabine and 1.31% to 1.88% and 3.34% to 6.98% for Cedazuridine, respectively. The analytes and IS were stable during all sample storage and analysis procedures.