Publication details

HPLC-FLD Method Development for the Determination of Alpelisib in Human Plasma

Authors

KREJČÍŘOVÁ Eva PELCOVÁ Marta JUŘICA Jan GLATZ Zdeněk

Year of publication 2023
Type Conference abstract
MU Faculty or unit

Faculty of Science

Citation
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).

You are running an old browser version. We recommend updating your browser to its latest version.

More info