Quantification of sorafenib, lenvatinib, and apatinib in human plasma for therapeutic drug monitoring by UPLC-MS/MS

Ye, Zhenjie; Wu, Lingjie; Zhang, Xiaoying; Hu, Yingying; Zheng, Ling

doi:10.1016/j.jpba.2021.114161

Cited by 14 publications

(16 citation statements)

References 29 publications

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“…The IS normalized matrix effect was 1.27±0.03 (SD) with a CV% ≤ 2.8% for QCL and 1.09±0.02 (SD) for QCH with a CV% ≤ 2.1. These data are slightly higher than previously published methods based on PP but with a much lower CV% [ 10 , 12 , 13 ]. The obtained CV% values were lower than the guidelines acceptance criteria (<15%) and so the matrix effect was considered negligible in affecting analyses results.…”

Section: Resultscontrasting

confidence: 54%

“…The percentage of LENVA recovery resulted high, ≥ 95.6% (range from 95.6 to 102, CV% ≤ 4.6), and reproducible over the concentrations ranges tested ( Table 3 ). These percentages are the highest (89.5%) among the published methods ( Table 1 ) based on the same sample treatment (PP) [ 7 , 9 , 12 , 13 ].…”

Section: Resultsmentioning

confidence: 99%

“…Even if the ISR is not requested by FDA guideline, we considered it an important test to verify the method reproducibility in “real” samples. Anyway, only the method proposed by Ye et al [ 13 ] performed the ISR on 24 clinical samples with a very good %difference (-4.5% to 3.1%).…”

Section: Resultsmentioning

confidence: 99%

“…In the literature three other methods were reported for LENVA quantification with other 8, 9 or 2 kinase inhibitors, respectively [ 10 , 12 , 13 ]. These methods overcome the above-mentioned limitations: they required a small sample volume (50/100 μL), had a fast chromatographic run (between 3.5 and 7min) and a simple sample preparation (PP).…”

Section: Introductionmentioning

confidence: 99%

“…These methods overcome the above-mentioned limitations: they required a small sample volume (50/100 μL), had a fast chromatographic run (between 3.5 and 7min) and a simple sample preparation (PP). Concentration ranges were suitable for the target C min of 51.5 ng/mL with the exception of the method developed by Ye et al [ 13 ] (1.25–40 ng/mL).…”

Section: Introductionmentioning

confidence: 99%

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A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring

et al. 2021

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Lenvatinib (LENVA) is an oral antineoplastic drug used for the treatment of hepatocellular carcinoma and thyroid carcinoma. LENVA therapeutic drug monitoring (TDM) should be mandatory for a precision medicine to optimize the drug dosage. To this end, the development of a sensitive and robust quantification method to be applied in the clinical setting is essential. The aim of this work was to develop and validate a sensitive, rapid, and cost-effective LC-MS/MS method for the quantification of LENVA in human plasma. On this premise, sample preparation was based on a protein precipitation and the chromatographic separation was achieved on a Synergi Fusion RP C18 column in 4 min. The method was completely and successfully validated according to European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines, with good linearity in the range of 0.50–2000 ng/mL (R≥0.9968). Coefficient of variation (CV) for intra- and inter-day precision was ≤11.3% and accuracy ranged from 96.3 to 109.0%, internal standard normalized matrix effect CV% was ≤2.8% and recovery was ≥95.6%. Successful results were obtained for sensitivity (signal to noise (S/N) ratio >21) and selectivity, dilution integrity (CV% ≤ 4.0% and accuracy 99.9–102%), and analyte stability under various handling and storage conditions both in matrix and solvents. This method was applied to quantify LENVA in patient’s plasma samples and covered the concentration range achievable in patients. In conclusion, a sensitive and robust quantification method was developed and validated to be applied in the clinical setting.

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Section: Resultscontrasting

confidence: 54%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring

et al. 2021

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Treatment of hepatocellular carcinoma with autologous platelets encapsulating sorafenib or lenvatinib: A novel therapy exploiting tumor‐platelet interactions

Tanaka

Horioka

Hasebe

et al. 2021

Intl Journal of Cancer

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Hepatocellular carcinoma (HCC) activates platelets through the action of adjacent sinusoidal cells. Activated platelets bind to tumor-associated endothelial cells and release growth factors that promote tumor progression. We hypothesized that platelets encapsulated with tumor inhibitors would function as drug carriers for tumor therapy. We propose a therapeutic strategy for HCC using autologous platelets encapsulating multiple tyrosine kinase inhibitors in a rat chemically induced HCC model. Sorafenib or lenvatinib was encapsulated in platelets isolated from tumor-bearing rats in vitro. The rats were divided into groups that received repeated intravenous injections (twice a week for 10 weeks) of the following materials: placebo, sorafenib (SOR), lenvatinib (LEN), autologous platelets, autologous platelets encapsulating sorafenib (SOR-PLT) and autologous platelets encapsulating lenvatinib (LEN-PLT). The therapeutic effect was then analyzed by ultrasonography (US) and histopathological analysis. Histopathological and US analysis demonstrated extensive tumor necrosis in the tumor tissue of SOR-PLT or LEN-PLT, but not in other experimental groups.By liquid chromatography-mass spectrometry, more abundant sorafenib was detected in tumor tissues after SOR-PLT administration than in surrounding normal tissues, but no such difference in sorafenib level was observed with SOR administration. Therefore, the use of autologous platelets encapsulating drugs might be a novel therapeutic strategy for HCC.

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Population Pharmacokinetic Modeling of Lenvatinib in Chinese Patients With Advanced Hepatocellular Carcinoma Using Real‐World Data

Chen

et al. 2022

The Journal of Clinical Pharma

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Lenvatinib is a novel oral angiogenesis inhibitor approved in China for the treatment of unresectable hepatocellular carcinoma (HCC) without prior systemic treatment. We described the population pharmacokinetics of lenvatinib in Chinese patients with advanced HCC and explore the potential patient characteristics associated with lenvatinib pharmacokinetics using real‐world data. A total of 266 samples, provided by 127 Chinese patients with advanced HCC, were analyzed by nonlinear mixed‐effects modeling. Monte Carlo simulation was conducted to assess impact of covariates on the exposure to lenvatinib. The clearance of lenvatinib in Chinese patients with advanced HCC was 5.3 L/h, and alkaline phosphatase, total bilirubin, and sex were identified as important covariates associated with it. The clearance of Child‐Pugh class B patients (4.82L/h) was significantly lower than that of Child‐Pugh class A patients (5.53 L/h), and the systemic exposure increased with the increase of alkaline phosphatase and total bilirubin. There were sex differences in the pharmacokinetic characteristics of lenvatinib. The clearance of women was significantly lower than that of men (4.61 vs 5.6 L/h; P < .001), and the area under the plasma concentration–time curve of women was ≈20% higher than that of men. In this study, a population pharmacokinetic model of lenvatinib was established, which can be used to simulate clinical trials or various dosing scenarios. Our findings provide important new insights for optimizing the use of lenvatinib in patients with advanced HCC.

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Quantification of sorafenib, lenvatinib, and apatinib in human plasma for therapeutic drug monitoring by UPLC-MS/MS

Cited by 14 publications

References 29 publications

A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring

A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring

Treatment of hepatocellular carcinoma with autologous platelets encapsulating sorafenib or lenvatinib: A novel therapy exploiting tumor‐platelet interactions

Population Pharmacokinetic Modeling of Lenvatinib in Chinese Patients With Advanced Hepatocellular Carcinoma Using Real‐World Data

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