Abstract
A new, rapid, and specific ultra performance liquid chromatographic assay with mass spectrometric detection has been developed and validated for the quantitative determination of the antiangiogenic agent lenalidomide in rat plasma using thalidomide as an internal standard with electro spray ionization in multiple-reaction monitoring mode. The analyte and internal standard were extracted by liquid–liquid extraction using methyl-tert-butyl ether solvent. Chromatography was performed isocratically on Acquity BEH C18 column using a mobile phase consisting of a mixture of buffer, acetonitrile, and formic acid in ratios of 30:70:0.1 (v/v/v). The method had a chromatographic run time of 1.2 min. The calibration curve was fit to a linear response concentration data over a range of 0.06–60.00 μM using a weighting factor of 1/×2. The intra- and inter-day precision and accuracy results were well within the acceptable limits. The validated method was successfully applied for routine analysis of the pharmacokinetics of lenalidomide.
Similar content being viewed by others
References
Ayalew T, Jorge C, Srdan V, Ruben AM, Deborah T, Terra LL, William JH, Mark RL, Jacob BA, Dan J, Catriona B, Jerome BZ, Rhett PK, Rebecca FM, Francis G, Hagop MK (2006) Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood 108:1158–1164
Barlogie B, Shaughnessy J, Tricot G, Jacobson J, Zangari M, Anaissie E, Walker R, Crowley J (2004) Treatment of multiple myeloma. Blood 103:20–32
Chanan-Khan A, Miller KC, Musial L, Lawrence D, Padmanabhan S, Takeshita K, Porter CW, Goodrich DW, Bernstein ZP, Wallace P, Spaner D, Mohr A, Byrne C, Hernandez-Ilizaliturri F, Chrystal C, Starostik P, Czuczman MS (2006) Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. J Clin Oncol 24:5343–5349
Dispenzieri A, Lacy MQ, Zeldenrust SR (2007) The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood 109:465–470
Kastritis E, Dimopoulos MA (2007) The evolving role of lenalidomide in the treatment of hematologic malignancies. Expert Opin Pharmacother 8:497–509
List A, Kurtin S, Roe DJ (2005) Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 352:549–557
List A, Dewald G, Bennett J (2006) Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 355:1456–1465
Mitsiades CS, Mitsiades N (2004) CC-5013 (Celgene). Curr Opin Investig Drugs 17:635–647
Nianhang C, Lian W, Henry L, Sekhar S, Gondi K (2012) Pharmacokinetics, metabolism and excretion of [(14)C]-lenalidomide following oral administration in healthy male subjects. Cancer Chemother Pharmacol 69:789–797
Rajkumar SV, Hayman SR, Lacy MQ, Dispenzieri A, Kabat SMGB, Zeldenrust SR, Kumar S, Greipp PR, Fonseca R, Lust JA, Russell SJ, Kyle RA, Witzig TE, Gertz MA (2005) Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 106:4050–4053
Richardson PG, Blood E, Mitsiades CS, Jagannath S, Zeldenrust SR, Alsina M, Schlossman RL, Rajkumar SV, Desikan KR, Hideshima T, Munshi NC, Kelly-Colson K, Doss D, McKenney ML, Gorelik S, Warren D, Freeman A, Rich R, Wu A, Olesnyckyj M, Wride K, Dalton WS, Zeldis J, Knight R, Weller E, Anderson KC (2006) A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 108:3458–3464
Robert K, Judah F (2002) Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2:727–739
Tohnya TM, Hwang K, Lepper ER (2004) Determination of CC-5013, an analogue of thalidomide, in human plasma by liquid chromatography-mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 811:135–141
Vaishali S, Daniel GW, Michael R, Kathleen TF, Salli F, Jerome BZ, Martha S, David CS (2007) Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trials. Blood 109:492–496
Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE, Lam W, McBride K, Wride K, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Habermann TM (2008) Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin’s lymphoma. J Clin Oncol 26:4952–4957
Witzig TE, Vose J, Pietronigro D (2007) J Clin Oncology 18:445–457
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Pocha, K., Devala Rao, G. Rapid determination of lenalidomide in rat plasma by an ultra performance liquid chromatography/tandem mass spectrometric method. Med Chem Res 24, 459–467 (2015). https://doi.org/10.1007/s00044-014-1106-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00044-014-1106-x