DEVELOPMENT AND VALIDATION OF LIQUID CHROMATOGRAPHY COUPLED WITH TANDEM MASS SPECTROMETRY METHOD FOR ESTIMATION OF LENVATINIB IN HUMAN PLASMA
DOI:
https://doi.org/10.22159/ajpcr.2017.v10i7.18287Keywords:
Lenvatinib, Validation, Analysis, NilAbstract
Objective: This study was to develop and validate a liquid chromatography–tandem mass spectrometry (LC–MS/MS) for the quantification of lenvatinib (LT) in human plasma.
Methods: A simple, sensitive and specific LC–MS/MS method was developed for quantification of LT in human plasma using LTD4 as internal standard (IS). The analytical method consists of liquid–liquid extraction of plasma sample followed by the determination of LT by a LC–MS/MS. The analyte was separated on a Zorbax Eclipse XDB-C18 (150×4.6 mm, 5 μ) column with an isocratic mobile phase of acetontrile:0.1% formic acid (80:20 v/v) at a flow rate of 0.6 mL/minutes. The protonated ions were formed by a turbolon spray in a positive mode were used to detect analyte and IS. The MS/MS detection was made by monitoring the fragmentation of m/z 427.10→370.10 for LT and m/z 430.30→370.10 for IS on a MS.
Result: The method was validated with the correlation coefficients of (r2) ≥0.995 over a linear concentration range of 10.20-501.60 pg/mL. This method demonstrated intra- and inter-day precision within 1.06-2.42% and 0.03-0.55% and accuracy within 95.64-100.08% and 97.16-100.07%.
Conclusion: This method is suitable and convenient to pharmacokinetics and bioavailability studies for estimation of LT in biological samples by LC–MS/MS.
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References
Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 2015;372(7):621-30.
Cabanillas ME, Schlumberger M, Jarzab B, Martins RG, Pacini F, Robinson B, et al. A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated thyroid cancer: A clinical outcomes and biomarker assessment. Cancer 2015;121(16):2749-56.
Krajewska J, Kukulska A, Jarzab B. Drug safety evaluation of lenvatinib for thyroid cancer. Expert Opin Drug Saf 2015;14(12):1935-43.
Cabanillas ME, Habra MA. Lenvatinib: Role in thyroid cancer and other solid tumors. Cancer Treat Rev 2016;42:47-55.
Nair A, Lemery SJ, Yang J, Marathe A, Zhao L, Zhao H, et al. FDA approval summary: Lenvatinib for progressive, radio-iodine-refractory differentiated thyroid cancer. Clin Cancer Res 2015;21(23):5205-8.
Yeung KT, Cohen EE. Lenvatinib in advanced, radioactive iodine-refractory, differentiated thyroid carcinoma. Clin Cancer Res 2015;21(24):5420-6.
Costa R, Carneiro BA, Chandra S, Pai SG, Chae YK, Kaplan JB, et al. Spotlight on lenvatinib in the treatment of thyroid cancer: Patient selection and perspectives. Drug Des Devel Ther 2016;10:873-84.
Cserhati T, Szogyi M. Chromatography of anticancer drugs. Eur Chem Bull 2013;2(10):715-21.
Prashanthi Y, Ahmed MA, Vijaya K, Riyazuddin. Method development and validation of lenvatinib drug by RP-HPLC in pharmaceutical drug dosage form. Indo Am J Pharm Sci 2016;3(10):1078-85.
Mano Y, Kusano K. A validated LC-MS/MS method of total and unbound lenvatinib quantification in human serum for protein binding studies by equilibrium dialysis. J Pharm Biomed Anal 2015;114:82-7.
Dubbelman AC, Rosing H, Thijssen B, Gebretensae A, Lucas L, Chen H, et al. Development and validation of LC-MS/MS assays for the quantification of E7080 and metabolites in various human biological matrices. J Chromatogr B Analyt Technol Biomed Life Sci 2012;887- 888:25-34.
Dubbelman AC, Rosing H, Nijenhuis C, Huitema AD, Mergui- Roelvink M, Gupta A, et al. Pharmacokinetics and excretion of (14) C-lenvatinib in patients with advanced solid tumors or lymphomas. Invest New Drugs 2015;33:233-40.
Shumaker RC, Aluri J, Fan J, Martinez G, Thompson GA, Ren M. Effect of rifampicin on the pharmacokinetics of lenvatinib in healthy adults. Clin Drug Investig 2014;34(19):651-9.
Shumaker R, Aluri J, Fan J, Martinez G, Pentikis H, Ren M. Influence of hepatic impairment on lenvatinib pharmacokinetics following single-dose oral administration. J Clin Pharmacol 2015;55(3):317-27.
Okamoto K, Kodama K, Takase K, Sugi NH, Yamamoto Y, Iwata M, et al. Antitumor activities of the targeted multi-tyrosine kinase inhibitor lenvatinib (E7080) against RET gene fusion-driven tumor models
Cancer Lett 2013;340(1):97-103.
Department of Health and Human Services. Guidance for Industry. Bio-Analytical Method Validation. Rockville, MD: U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER); 2001.
Singhal P, Shah PA, Shah JV, Sanyal M, Shrivastav PS. Sensitive and rapid estimation of lapatinib, an anticancer drug in spiked human plasma by LC-MS/MS. Int J Pharm Pharm Sci 2016;8(1):214-20.
Singhal P, Shah PA, Shah JV, Sharma P, Shrivastav PS. Determination of capecitabine-an anticancer drug in dried blood spot by LC-ESI-MS/MS. Int J Pharm Pharm Sci 2015;7(12):238-45.
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