HPLC-FLD Method Development for the Determination of Alpelisib in Human Plasma
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| Year of publication | 2023 |
| Type | Conference abstract |
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| Description | Alpelisib (ALP) is a selective phosphatidylinositol 3-kinase (PI3K) inhibitor approved for breast cancer treatment. Dysregulation of the PI3K signal pathway is involved in progression of cancer and is therefore a target for antineoplastic therapy. Another indication approved only in the United States is the treatment of severe manifestations of PIK3CA-Related Overgrowth Spectrum, including venous malformations. ALP exposure shows considerable inter-individual variability and adverse effects and therefore therapeutic drug monitoring (TDM) is beneficial. Fluorescence detection is a more affordable alternative to LC-MS/MS methods and provides sufficient sensitivity for TDM and pharmacokinetic profiling. After optimizing the HPLC-FLD separation conditions, a suitable liquid-liquid extraction procedure was tested. The highest extraction yield was obtained with a mixture of dichloromethane-isopropanol, 9:1 (v/v). The method was validated according to the European Medicines Agency guidelines. The developed HPLC-FLD method was applied to determine ALP in patient plasma samples. The obtained concentrations were within the chosen calibration range (10–1000 ng/mL). This method is sensitive enough for the TDM of ALP in human plasma even for non-standard dosing schedules (e.g. off label use, children). |