A validated LC–MS/MS method of total and unbound lenvatinib quantification in human serum for protein binding studies by equilibrium dialysis

Mano, Yoshihiro; Kusano, Kazutomi

doi:10.1016/j.jpba.2015.05.008

Cited by 30 publications

(19 citation statements)

References 9 publications

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“…The results are in accordance with two previous studies by using ER-227326-00 as an internal standard presented by Dubbelman et al [5] and Mano and Kusano [6]. …”

Section: Resultssupporting

confidence: 93%

“…Two studies on development and validation of the quantification method of lenvatinib by liquid chromatography-tandem mass spectrometry (LC-MS/MS) have been reported previously [5, 6]. These studies used ER-227326 (IUPAC: 4-{3-chloro-4-[(propylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxamide) monomethanesulfonate, which is synthesized by Eisai Inc. as an internal standard.…”

Section: Introductionmentioning

confidence: 99%

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Validation of a Liquid Chromatography-Tandem Mass Spectrometric Assay for Quantitative Analysis of Lenvatinib in Human Plasma

Ogawa-Morita

Sano

Okano

et al. 2017

International Journal of Analytical Chemistry

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Toward conducting clinical pharmacokinetic studies of an antineoplastic agent, lenvatinib, we developed a liquid chromatography-tandem mass spectrometric assay for its quantitative analysis in human plasma. Analyte (lenvatinib) and internal standard (IS, propranolol) in the plasma were extracted by using acetonitrile and chromatographically separated by using a XTerra MS C18 column with 0.2 mL/min flow and mobile phase starting with 0.1% formic acid in water, followed by increasing percentage of acetonitrile. Detection was performed by using combined reversed-phase liquid chromatography-tandem mass spectrometry (LC/MS-MS) with positive ion electrospray ionization. MS-MS ion transitions used were 427.602>371.000 for lenvatinib and 260.064>116.005 for IS. This study was validated for accuracy, precision, linearity, range, selectivity, lower limit of quantification, recovery, and matrix effect according to the Guideline on Bioanalytical Method Validation in Pharmaceutical Development in Japan. Calibration curve was plotted by using lenvatinib concentrations ranging within 9.6–200 ng/mL, and correlation coefficients (r2) were in excess of 0.997. Intra- and interday accuracy ranged within 95.8–108.3% with mean recoveries of 66.8% for lenvatinib, and precision was <6.7% at all quality control concentration levels. Matrix effect analysis showed extraction efficiency of 15.7% for lenvatinib. Collectively, these findings demonstrate the feasibility of this method to evaluate kinetic disposition of lenvatinib.

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“…The results are in accordance with two previous studies by using ER-227326-00 as an internal standard presented by Dubbelman et al [5] and Mano and Kusano [6]. …”

Section: Resultssupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Validation of a Liquid Chromatography-Tandem Mass Spectrometric Assay for Quantitative Analysis of Lenvatinib in Human Plasma

Ogawa-Morita

Sano

Okano

et al. 2017

International Journal of Analytical Chemistry

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“…AEs were graded according to the National Cancer Institute Common Terminology Criteria for AEs, version 3.0. A pre-dose blood sample was obtained for pharmacokinetic (PK) assessment on days 1, 8, 15, and 22 of cycle 1, and day 1 of cycles 2 and 3, using a validated liquid chromatography–tandem mass spectrometry method [19]. …”

Section: Methodsmentioning

confidence: 99%

Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma

et al. 2016

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BackgroundLenvatinib is an oral inhibitor of vascular endothelial growth factor receptor 1–3, fibroblast growth factor receptor 1–4, platelet-derived growth factor receptor alpha, RET, and KIT. This phase 2, single-arm, open-label multicenter study evaluated lenvatinib in advanced hepatocellular carcinoma (HCC).MethodsPatients with histologically/clinically confirmed advanced HCC who did not qualify for surgical resection or local therapies received lenvatinib at a dosage of 12 mg once daily (QD) in 28-day cycles. The primary efficacy endpoint was time to progression (TTP) per modified Response Evaluation Criteria in Solid Tumors v1.1; secondary efficacy endpoints included objective response rate (ORR), disease control rate (DCR), and overall survival (OS).ResultsBetween July 2010 and June 2011, 46 patients received lenvatinib at sites across Japan and Korea. The median TTP, as determined by independent radiological review, was 7.4 months [95 % confidence interval (CI): 5.5–9.4]. Seventeen patients (37 %) had partial response and 19 patients (41 %) had stable disease (ORR: 37 %; DCR: 78 %). Median OS was 18.7 months (95 % CI: 12.7–25.1). The most common any-grade adverse events (AEs) were hypertension (76 %), palmar-plantar erythrodysesthesia syndrome (65 %), decreased appetite (61 %), and proteinuria (61 %). Dose reductions and discontinuations due to AEs occurred in 34 (74 %) and 10 patients (22 %), respectively. Median body weight was lower in patients with an early (<30 days) dose withdrawal or reduction than in those without.ConclusionsLenvatinib 12-mg QD showed clinical activity and acceptable toxicity profiles in patients with advanced HCC, but early dose modification was necessary in patients with lower body weight. Further development of lenvatinib in HCC should consider dose modification by body weight.Trial registration ID www.ClinicalTrials.gov NCT00946153.Electronic supplementary materialThe online version of this article (doi:10.1007/s00535-016-1263-4) contains supplementary material, which is available to authorized users.

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“…Various analytical techniques that have been used to characterize biomolecular interactions. Some of these techniques include affinity-based separation techniques, which represent the major domain of affinity chromatography, [4][5][6] and affinity capillary electrophoresis [7][8][9] as well as equilibrium dialysis, which is still interesting and widely used especially in drug-protein interaction studies [10][11][12]. On the other hand, biochemical and biophysical techniques are attractive and developed dramatically to be the first choice in studying biomolecular interactions.…”

Section: Introductionmentioning

confidence: 99%

Thermophoresis for characterizing biomolecular interaction

Asmari

Ratih

Alhazmi

et al. 2018

Methods

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The study of biomolecular interactions is crucial to get more insight into the biological system. The interactions of protein-protein, protein-nucleic acids, protein-sugars, nucleic acid-nucleic acids and protein-small molecules are supporting therapeutics and technological developments. Recently, the development in a large number of analytical techniques for characterizing biomolecular interactions reflect the promising research investments in this field. In this review, microscale thermophoresis technology (MST) is presented as an analytical technique for characterizing biomolecular interactions. Recent years have seen much progress and several applications established. MST is a powerful technique in quantitation of binding events based on the movement of molecules in microscopic temperature gradient. Simplicity, free solutions analysis, low sample volume, short analysis time, and immobilization free are the MST advantages over other competitive techniques. A wide range of studies in biomolecular interactions have been successfully carried out using MST, which tend to the versatility of the technique to use in screening binding events in order to save time, cost and obtained high data quality.

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A validated LC–MS/MS method of total and unbound lenvatinib quantification in human serum for protein binding studies by equilibrium dialysis

Cited by 30 publications

References 9 publications

Validation of a Liquid Chromatography-Tandem Mass Spectrometric Assay for Quantitative Analysis of Lenvatinib in Human Plasma

Validation of a Liquid Chromatography-Tandem Mass Spectrometric Assay for Quantitative Analysis of Lenvatinib in Human Plasma

Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma

Thermophoresis for characterizing biomolecular interaction

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