Validation of high-performance liquid chromatography-tandem mass spectrometry assays quantifying omacetaxine mepesuccinate and its 4 '-des-methyl and cephalotaxine metabolites in human plasma and urine

摘要

Omacetaxine mepesuccinate (hereafter called omacetaxine) is a modified cephalotaxine and is registered (Synribe (R)) for the treatment of adult patients with chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs). To evaluate the pharmacokinetics of omacetaxine, sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for the quantification of omacetaxine and its inactive 4'-des-methyl (4'-DMHHT) and cephalotaxine metabolites in human plasma and urine were developed and validated.