Development and validation of an UPLC-MS/MS method for the therapeutic drug monitoring of oral anti-hormonal drugs in oncology

摘要

A liquid chromatography-mass spectrometry assay was developed and validated for simultaneous quantification of anti-hormonal compounds abiraterone, anastrozole, bicalutamide, Δ(4)-abiraterone (D4A), N-desmethyl enzalutamide, enzalutamide, Z-endoxifen, exemestane and letrozole for the purpose of therapeutic drug monitoring (TDM).Plasma samples were prepared with protein precipitation.Analyses were performed with a triple quadrupole mass spectrometer operating in the positive and negative ion-mode.The validated assay ranges from 2 to 200 ng/mL for abiraterone, 0.2–20 ng/mL for D4A, 10–200 ng/mL for anastrozole and letrozole, 1–20 ng/ mL for Z-endoxifen, 1.88–37.5 ng/mL for exemestane and 1500–30,000 ng/mL for enzalutamide, N-desmethyl enzalutamide and bicalutamide.Due to low sensitivity for exemestane, the final extract of exemestane patient samples should be concentrated prior to injection and a larger sample volume should be prepared for exemestane patient samples and QC samples to obtain adequate sensitivity.Furthermore, we observed a batch-dependent stability for abiraterone in plasma at room temperature and therefore samples should be shipped on ice.This newly validated method has been successfully applied for routine TDM of anti-hormonal drugs in cancer patients.