Development and validation of a highly sensitive liquid chromatography/mass spectrometry method for simultaneous quantification of lenalidomide and flavopiridol in human plasma.

摘要: Lenalidomide, an immunomodulatory agent, and flavopiridol, a broad cyclin-dependent kinase inhibitor, are active therapies for clinical use in genomic high-risk chronic lymphocytic leukemia. A high-performance liquid chromatographic assay with tandem mass spectrometric detection has been developed to simultaneously quantify lenalidomide flavopiridol human mouse plasma facilitate their combined development. Samples were prepared by liquid-liquid extraction acetonitrile (ACN)-containing internal standard, genistein, followed evaporation of solvent reconstitution 95/5 H2O/ACN. Lenalidomide standard separated reversed-phase chromatography on C-18 column using gradient H2O ACN, each 0.1% formic acid. Atmospheric pressure chemical ionization positive ion mode single reaction monitoring triple quadrupole spectrometer was applied detect transitions (260.06 > 149.10) (402.09 341.02). Lower limits quantification 1 0.3 nM, respectively. Recoveries from ranged 99% 116% throughout linear ranges. Within- between-run precision accuracy replicate samples all less than 15%. This is the most sensitive analytical method reported date both flavopiridol. sensitivity will enable late terminal phase concentration measurements accurate pharmacokinetic parameter estimation planned trial patients