Quantification of Tofacitinib in Human Plasma Samples Using Radio-Labeled Internal Standard

Abstract

A simple, sensitive and accurate liquid chromatography tandem mass spectrometric method has been developed and validated for determination of Tofacitinib in human plasma. The method was developed on Agilent Zorbax SB-C8 150×4.6 mm, 5 µm column using 10mM ammonium formate: acetonitrile (40:60 v/v) mobile phase for Chromatographic separation of Tofacitinib. The Tofacitinib and Tofacitinib- C3 were monitored by electrospray ionization in positive ion multiple reactions monitoring mode to detect the Tofacitinib at mass/charge 313.200/149.200 and Tofacitinib-13C3 (Internal Standard) at 316.500/149.200. Liquid-liquid extraction was employed in the extraction of analytes from human plasma. Both drug and internal standards were stable in plasma samples. The proposed method was validated as per international council of harmonization guidelines over a linear concentration range of 0.2ng/mL to 100.0ng/mL with a correlation coefficient (r) of ≥ 0.9983. Bioavailability and Bioequivalence studies of tofacitinib in biological samples can be achieved by analyzing them using the validated developed method. This study plays a key role in determining routine therapeutic drug monitoring of tofacitinib drug.