Highly sensitive ultra-performance liquid chromatography–tandem mass spectrometry method for the determination of abiraterone in human plasma

Abstract

Abiraterone (ABR) is a rationally designed CYP17 inhibitor that blocks the conversion of androgens from non-gonadal precursors effectively, thus reducing testosterone to undetectable levels. With the objective of reducing analysis time and maintaining good efficiency, there has been substantial focus on high-speed chromatographic separations, and ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) is a pre-eminent analytical tool for rapid biomedical analysis. In this study a rapid and precise UPLC–MS/MS method has been developed and validated for the determination of ABR in plasma. After a simple protein precipitation using methanol, ABR and carbamazepine (internal standard; IS) were separated on an Acquity UPLC BEH™ C₁₈ column (50 × 2.1 mm, i.d. 1.7 μm, Waters, USA) using a mobile phase of acetonitrile : water : formic acid (90 : 10 : 0.1%, v/v/v) pumped at a flow rate of 0.3 mL min⁻¹. ABR and IS were eluted at 0.61 and 0.48 min, respectively. The mass spectrometric determination was carried out using an electrospray interface operated in the positive mode with multiple reaction monitoring (MRM) mode. The precursors to product ion transitions of m/z 350.1 > 156.0, and m/z 237.0 > 179.0 were used to quantify ABR and IS, respectively and m/z 350.1 > 170.0 transition was used as the qualifying ion for ABR. The method was linear in the concentration range of 0.1–50 ng mL⁻¹ with good correlation coefficient of (0.995) and with a limit of quantitation of 0.1 ng mL⁻¹. The intra- and inter-assay precisions were satisfactory; the relative standard deviations did not exceed 13.29%. The accuracy of the method was proved; recoveries of ABR from spiked human plasma were 75.83–78.33%. The proposed UPLC–MS/MS method is simple, rapid and highly sensitive, and hence it could be reliable for pharmacokinetic and toxicokinetic studies in both animals and humans.