No abstract

Abiraterone acetate efficacy against prostate cancer is dependent on the circulating levels of abiraterone and its active metabolites, which present significant pharmacokinetic variability among patients. Thus, therapeutic drug monitoring can be performed to improve treatment outcomes. To support such studies, there are only a limited number of bioanalytical methods in current literature. This work presents a fast method to quantify abiraterone and D4A in plasma in 4 min by UPLC-MS/MS. Bioanalytical method validation was performed according to the recommendations of the US Food and Drug Administration. The method was linear within the range of 1-400 ng/ml for abiraterone and 0.2-20 ng/ml for D4A (r 2 > 0.99). Based on the analysis of quality control samples at the lower limit of quantification, low, medium and high concentrations, the method was precise (CV abiraterone ≤ 9.72%; CV D4A ≤ 14.64%) and accurate (CV abiraterone 95.51-107.59%; CV D4A 98.04-99.89%). Application of the method to the quantification of abiraterone and D4A in 10 clinical samples revealed important variability in the conversion ratio of abiraterone to D4A (CV 90.85%). Considering the current literature, this is the fastest method to quantify abiraterone and D4A in plasma, allowing for optimization of the analytical routine. K E Y W O R D S abiraterone, bioanalytical method validation, D4A, therapeutic drug monitoring, UPLC-MS/MS 1 | INTRODUCTION Abiraterone [17-(3-pyridyl)-androsta-5,16-dien-3β-ol, C 24 H 31 NO], administered as the pro-drug abiraterone acetate, is an androgen synthesis inhibitor used to treat castration-resistant prostate cancer. The standard dose is 1,000 mg/day taken in fasted state in association with prednisone 10 mg/day (FDA, 2011). Clinical studies have provided evidence for the variable efficacy of treatment