Two high-performance liquid chromatography-tandem mass spectrometry methods for determination of edaravone and taurine in human plasma: Application to drug-drug interaction and pharmacokinetic studies.
Two high-performance liquid chromatography-tandem mass spectrometry methods were developed and validated for the quantification of edaravone (method A) or taurine (method B) in human plasma. After protein precipitation, separations were achieved on an Ultimate XB-C8 (2.1 × 50 mm, 3.0 µm) column for edaravone and a ZORBAX SB-Aq column (2.1 × 100 mm, 3.5 µm) for taurine, respectively. The detection used electrospray ionization source via multiple reaction monitoring in positive-ion mode for edaravone and negative-ion mode for taurine, respectively. The lower limits of quantification were 10.0 ng/mL for edaravone and 3.00 μg/mL for taurine. The selectivity, accuracy, and precision of the methods were all within acceptable limits. Two methods were successfully applied to a drug-drug interaction study and a pharmacokinetic study of edaravone and taurine in healthy Chinese volunteers after intravenous infusion of single or compound injection. The results showed that co-administration of edaravone with taurine increased the Cmax and AUC0-24 of taurine in human plasma while taurine did not affect the systemic exposure of edaravone. Edaravone and taurine have the dose-dependent pharmacokinetic profiles in human.