A quick UPLC-MS/MS method for therapeutic drug monitoring of abiraterone and delta(4)-abiraterone in human plasma.

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 (r2  > 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 (CVabiraterone  ≤ 9.72%; CVD4A  ≤ 14.64%) and accurate (CVabiraterone 95.51-107.59%; CVD4A 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.

• Authors: Thaís Luise Dillenburg Weiss, Carolina Mesquita Furtado, Marina Venzon Antunes, Gustavo Gössling, Gilberto Schwartsmann, Rafael Linden, Simone Gasparin Verza
• Journal: Biomedical chromatography : BMC (Biomed Chromatogr) Vol. 34 Issue 11 Pg. e4947 (Nov 2020) ISSN: 1099-0801 [Electronic] England
• PMID: 32652651 (Publication Type: Journal Article)
• Copyright: © 2020 John Wiley & Sons, Ltd.

Chemical References

• Androstenes
• delta4-abiraterone
• abiraterone

Topics

• Androstenes (blood, chemistry, pharmacokinetics)
• Chromatography, High Pressure Liquid (methods)
• Drug Monitoring (methods)
• Humans
• Limit of Detection
• Linear Models
• Reproducibility of Results
• Tandem Mass Spectrometry (methods)