Simultaneous determination of canrenone, digoxin and tolvaptan by UHPLC–MS/MS: application in heart failure patients

Aim: Heart failure patients are frequently given comedication of digoxin and diuretics like spironolactone and tolvaptan. A UHPLC–MS/MS assay for determining canrenone (main active metabolite of spironolactone), digoxin and tolvaptan simultaneously should be developed so as to support related drug–drug interaction studies. Results: A UHPLC–MS/MS method for simultaneous determination of these three drugs in human plasma was established and fully verified as per CFDA guidelines. Chromatographic separation was achieved using a 4-min isocratic elution. Mass analyses were performed under positive electrospray ionization mode. The calibration curves were established over 1.0–400.0 ng/ml for canrenone and tolvaptan while over 0.1–40.0 ng/ml for digoxin. Conclusion: The developed method was feasible in detecting concentration and related drug–drug interaction studies.