DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Development and Validation of a Highly Sensitive Liquid Chromatography/Mass Spectrometry Method for Simultaneous Quantification of Lenalidomide and Flavopiridol in Human Plasma.

Author(s): Liu Q, Farley KL, Johnson AJ, Muthusamy N, Hofmeister CC, Blum KA, Schaaf LJ, Grever MR, Byrd JC, Dalton JT, Phelps MA

Affiliation(s): From the *Division of Pharmaceutics, College of Pharmacy, daggerComprehensive Cancer Center, double daggerDivision of Hematology-Oncology, Department of Internal Medicine, and section signDivision of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio.

Publication date & source: 2008-08-14, Ther Drug Monit., [Epub ahead of print]

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- and between-run precision and accuracy of replicate samples were all less than 15%. This is the most sensitive analytical method reported to date for both lenalidomide and flavopiridol. This sensitivity will enable late terminal phase concentration measurements and accurate pharmacokinetic parameter estimation in a planned clinical trial with lenalidomide and flavopiridol in patients with chronic lymphocytic leukemia.

Page last updated: 2008-11-03

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017