Comparative Analysis of Plasma and Dried Plasma Spots (DPS) of Tofacitinib-A Pan JAK inhibitor using LC-MS/MS; Application to Pharmacokinetic Study in Mice

Dried plasma spots were employed as an alternative sample collection technique for the quantitative determination of tofacitinib in mice plasma, using liquid chromatography tandem mass spectrometry method. Method: A simple, highly sensitive and rapid assay method has been developed for the estimation of tofacitinib on mice dried plasma spots (DPS) using liquid chromatography attached to tandem mass spectrometry with electro spray ionization (ESI) in the positive-ion mode. The method employs liquid extraction of tofacitinib from DPS disk of mice dried plasma spots followed by chromatographic separation using 5 mM ammonium formate with 0.1% Formic acid in water: acetonitrile in gradient elution method at a flow rate of 0.350 mL/min on an Acquity UPLC BEH C18 (50 x 2.1 mm, 1.7 µm) column with a total run time 2.5 min. The MS/MS ion transitions monitored were m/z 313→149 for tofacitinib and m/z 477→210 for the internal standard (Loperamide). Result: The assay was linear in the range of 1.16–1511 ng/mL. In current study this new method has been applied to analyze the DPS (Dried Plasma Spot) and neat plasma samples of Tofacitinib obtained from a pharmacokinetic study in mice. Conclusion: The quantitative analysis of tofacitinib with dried plasma spot specimens seems to be a prominent and advantageous technique, especially when applied to pharmacokinetic studies, where plasma sampling procedure becomes rapid and required plasma volumes are negligible and storage of samples is an issue