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- W2318982511 abstract "Background and objective: Lapatinib is a 4-anilinoquinazoline that can reversible and selectively inhibit both human epidermal growth factor receptor (EGFR, HER1) and human epidermal growth factor receptor type 2 (HER2) tyrosine kinases. As others tyrosine kinase inhibitors (TKIs), lapatinib shows a large interindividual variability in its pharmacokinetics (PK). So, the variability in drug exposure to TKIs may contribute to the variation in anti-cancer PD effect. Causes for this PK variability are manifold during the different processes of ADME. Up to date, only mass spectrometry detection is currently available to determine lapatinib in human plasma. The purpose of this study was to develop a simple and sensitive high-performance liquid chromatographic method with UV-Visible detection for quantification of lapatinib concentrations in human plasma to allow therapeutic drug monitoring (TDM) of lapatinib in cancer patients. Methods: After a liquid-liquid extraction with acetonitrile, lapatinib and sorafenib (internal standard, IS) are separated on Ultrabase C18 column using a mobile phase consisting of a mixture of 0.02 M ammonium acetate and acetonitrile in a proportion 47:53 pumped at a constant flow rate of 1.2 mL/min. The column was maintained at 25°C and the eluent was monitored at a wavelength of 260 nm. Results: The calibration curve was linear in the range 200-10000 ng/mL. The limit of quantification was determined to be 200 ng/mL. Lapatinib and IS retention times were 3.2 and 10.6 min, respectively. Inter- and intra-day coefficients of variation were less than 7%. The mean extraction recovery from plasma was higher than 86%. Conclusion: The simple, rapid and sensitive HPLC-UV method developed and validated for the measurement of lapatinib in human plasma using sorafenib as IS can be applied easily in routine clinical practice for the TDM of lapatinib. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 757. doi:1538-7445.AM2012-757" @default.
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- W2318982511 date "2012-04-15" @default.
- W2318982511 modified "2023-09-27" @default.
- W2318982511 title "Abstract 757: Development and validation of an HPLC-UV method for lapatinib quantification in human plasma" @default.
- W2318982511 doi "https://doi.org/10.1158/1538-7445.am2012-757" @default.
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