First data on alpelisib concentrations in plasma determined by HPLC-FLD method
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| Year of publication | 2024 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | Alpelisib (ALP) is a phosphatidylinositol 3-kinase (PI3K) inhibitor that is effective for the treatment of breast cancer with pathogenic PIK3CA variants. In 2022, the FDA approved alpelisib also for the treatment of patients with noncancerous PIK3CA-related overgrowth spectrum (PROS), including PIK3CA associated venous malformations. However, ALP exposure shows considerable inter-individual variability and, along with adverse effects, induces the necessity for therapeutic drug monitoring (TDM). In this study, ALP analysis was performed on an Agilent 1200 Series liquid chromatograph combined with a fluorescence detector. The excitation and emission wavelengths were set to 311 nm and 384 nm, respectively. A Kinetex Core-Shell C18 column (100 × 3 mm, 2.6 µm) heated to 40 °C was used for separation. The mobile phase consisted of ammonium acetate (10 mM, pH 6.6) and acetonitrile at 65:35 (v/v) in isocratic mode. The flow rate was 0.5 mL/min, and the total time of a single run was 8 min. Analytical data were processed using Agilent OpenLAB CDS software. The samples of plasma were obtained from the patients treated at the Children's Oncology Clinic of the University Hospital Brno upon subscription of Informed Consent by their parents or legal guardians. The study was approved by the Ethics Committee of the University Hospital Brno (Approval No.01-130923/EK). The developed HPLC-FLD method was applied to determine ALP in patient plasma samples. Quantification was based on the peak area ratio of the analyte to the IS, and the obtained concentrations were within the chosen calibration range (30–1000 ng/mL). The method is sensitive enough for the TDM of ALP in human plasma. The upcoming study will target its clinical utilization. This work was financially supported by the MUNI/A/1580/2023 project. |
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