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

Therapeutic Drug Monitoring
Qing LiuMitch A Phelps

Abstract

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 and flavopiridol in human and mouse plasma to facilitate their combined clinical development. Samples were prepared by liquid-liquid extraction with acetonitrile (ACN)-containing internal standard, genistein, followed by evaporation of solvent and reconstitution in 95/5 H2O/ACN. Lenalidomide and internal standard were separated by reversed-phase liquid chromatography on a C-18 column using a gradient of H2O and ACN, each with 0.1% formic acid. Atmospheric pressure chemical ionization in positive ion mode with single reaction monitoring on a triple quadrupole mass spectrometer was applied to detect transitions of lenalidomide (260.06 > 149.10) and flavopiridol (402.09 > 341.02). Lower limits of quantification of lenalidomide and flavopiridol were 1 and 0.3 nM, respectively. Recoveries of lenalidomide and flavopiridol from human plasma ranged from 99% to 116% throughout their linear ranges. Within...Continue Reading

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Citations

Nov 20, 2008·Current Treatment Options in Oncology·Peter H Wiernik
Aug 10, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Craig C HofmeisterMitch A Phelps
Jan 30, 2013·Expert Opinion on Pharmacotherapy·Peter H Wiernik
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Jul 15, 2016·Expert Opinion on Investigational Drugs·Sylvain GarciazRéda Bouabdallah
Jan 28, 2014·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Sridhar VeeraraghavanManivannan Rangasamy
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Sep 8, 2019·Cancer Chemotherapy and Pharmacology·Jim H HughesDavid J R Foster
Jul 14, 2016·AIDS Research and Human Retroviruses·Valérie PourcherDominique Costagliola

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