Simultaneous quantitative detection of afatinib, erlotinib, gefitinib, icotinib, osimertinib and their metabolites in plasma samples of patients with non-small cell lung cancer using liquid chromatography-tandem mass spectrometry

Xiong, Xin; Zhang, Yuanyuan; Wang, Ziyu; Zhou, Chen; Yang, Ping; Du, Xin; Yang, Li; Liu, Wei

doi:10.1016/j.cca.2021.12.028

Cited by 9 publications

(2 citation statements)

References 30 publications

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“…Meanwhile, other deuterated ISs (d6-HAS-000719) used in previous studies were not readily available . Furthermore, osimertinib, with a similar structure to almonertinib, was also tested, and we found that even 500 μl of TBME could not extract osimertinib completely, but a larger volume of TBME will lead to excessive use of organic reagent (Aghai-Trommeschlaeger et al, 2022;Xiong et al, 2022), which is not friendly to the environment. In this study, sorafenib-D 3 as an IS not only had remarkable stability and sensitivity, but also no significant matrix effect was observed at the retention time, which was consistent with the previous study .…”

Section: Methods Development and Optimizationmentioning

confidence: 99%

Effects of voriconazole and fluconazole on the pharmacokinetics of almonertinib in rats by UPLC–MS/MS

Liu

et al. 2022

Biomedical Chromatography

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Almonertinib was included in the first‐line treatment of non‐small cell lung cancer with EGFR T790M mutations by the Chinese Society of Clinical Oncology in 2021. Considering that immunocompromised lung cancer patients are prone to opportunistic fungal infections, and most triazole antifungal drugs are moderate or strong inhibitors of CYP3A4, this study was conducted to develop and validate an accurate and rapid ultra‐performance liquid chromatography tandem mass spectrometry method for quantifying almonertinib in plasma and for investigating the pharmacokinetic changes of almonertinib caused by voriconazole and fluconazole in rats. After liquid–liquid extraction with tert‐butyl methyl ether, an XSelect HSS T3 column (2.1 × 100 mm, 2.5 μm, Waters) was used for the chromatographic separation of almonertinib and sorafenib‐D3 (internal standard). The analytes were detected using an AB Sciex Triple Quad 5,500 mass spectrometer in the positive ionization mode. The method exhibited great linearity (0.5–200 ng/ml, r > 0.997) and stability under the established experimental conditions. All validation experiments were in accordance with the guidelines, and the results were all within the acceptable limits. This method was successfully applied to the researches of pharmacokinetics and drug interactions for almonertinib in rats. Voriconazole and fluconazole significantly altered the pharmacokinetic profiles of almonertinib and increased the systemic exposure of almonertinib in rats to different degrees, but further human trials should be conducted to validate the results.

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Section: Methods Development and Optimizationmentioning

confidence: 99%

Effects of voriconazole and fluconazole on the pharmacokinetics of almonertinib in rats by UPLC–MS/MS

Liu

et al. 2022

Biomedical Chromatography

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“…The osimertinib analysis in the matrix such as human serum, human plasma, human urine, rat plasma, and mouse brain has been constructed through liquid chromatography-tandem mass spectrometric (LC-MS) assay (Ballard et al, 2016;Rood et al, 2016;Irie et al, 2019;Mitchell et al, 2019;Fresnais et al, 2020;Xiong et al, 2022). However, the instability of osimertinib in plasma and whole blood at an ambient temperature drew attention recently.…”

Section: Introductionmentioning

confidence: 99%

Instability Mechanism of Osimertinib in Plasma and a Solving Strategy in the Pharmacokinetics Study

Yuan

et al. 2022

Front. Pharmacol.

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Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and a star medication used to treat non-small-cell lung carcinomas (NSCLCs). It has caused broad public concern that osimertinib has relatively low stability in plasma. We explored why osimertinib and its primary metabolites AZ-5104 and AZ-7550 are unstable in rat plasma. Our results suggested that it is the main reason inducing their unstable phenomenon that the Michael addition reaction was putatively produced between the Michael acceptor of osimertinib and the cysteine in the plasma matrix. Consequently, we identified a method to stabilize osimertinib and its metabolite contents in plasma. The assay was observed to enhance the stability of osimertinib, AZ-5104, and AZ-7550 significantly. The validated method was subsequently applied to perform the pharmacokinetic study for osimertinib in rats with the newly established, elegant, and optimized ultra-performance liquid chromatography–tandem mass spectrometer (UPLC-MS/MS) strategy. The assay was assessed for accuracy, precision, matrix effects, recovery, and stability. This study can help understand the pharmacological effects of osimertinib and promote a solution for the similar problem of other Michael acceptor-contained third-generation EGFR-TKI.

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Supramolecular fluorescence sensor array used for the analysis of tyrosine kinase inhibitors in biological fluids and cell imaging

Yi,

Yang,

Tang

et al. 2024

Analytica Chimica Acta

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Simultaneous quantitative detection of afatinib, erlotinib, gefitinib, icotinib, osimertinib and their metabolites in plasma samples of patients with non-small cell lung cancer using liquid chromatography-tandem mass spectrometry

Cited by 9 publications

References 30 publications

Effects of voriconazole and fluconazole on the pharmacokinetics of almonertinib in rats by UPLC–MS/MS

Effects of voriconazole and fluconazole on the pharmacokinetics of almonertinib in rats by UPLC–MS/MS

Instability Mechanism of Osimertinib in Plasma and a Solving Strategy in the Pharmacokinetics Study

Supramolecular fluorescence sensor array used for the analysis of tyrosine kinase inhibitors in biological fluids and cell imaging

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