Digoxin-d₃is intended for use as an internal standard for the quantification of digoxin by GC- or LC-MS. Digoxin is a cardiac glycoside and metabolite of digitoxin that binds to and inhibits the Na⁺/K⁺-ATPase in cardiac tissues in an ATP- and Mg²⁺-dependent manner.¹This inhibition results in loss of the transmembrane Na⁺gradient, which decreases activity of the Na⁺/Ca²⁺exchanger, increasing intracellular Ca²⁺levels, inotropy, and cardiac force.²It increases activity of mitochondrial ATPase and actomyosin ATPase in rat hearts, which is directly correlated with increased myofibrillar contractile strength.³In vivo, digoxin also decreases right atrial pressure and increases cardiac output in a canine model of congestive heart failure produced by pulmonary artery constriction.⁴Formulations containing digoxin have been used to treat atrial fibrillation.⁵

1.Matsui, H., and Schwartz, A.Mechanism of cardiac glycoside inhibition of the (Na+-K+)-dependent ATPase from cardiac tissueBiochim. Biophys. Acta.151(3)655-663(1968) 2.Neves, C.H., Tibana, R.A., Prestes, J., et al.Digoxin induces cardiac hypertrophy without negative effects on cardiac function and physical performance in trained normotensive ratsInt. J. Sports Med.38(4)263-269(2017) 3.Hamrick, M.E., and Fritz, P.J.Enzymatic adaptation: Molecular basis for cardiac glycoside action• 1. Increase in rat heart actomyosin and mitochondrial ATPase specific activities following digoxin injectionBiochem. Biophys. Res. Commun.22(5)540-546(1966) 4.Davis, J.O., Howell, D.S., and Hyatt, R.E.Effects of acute and chronic digoxin administration in dogs with right-sided congestive heart failure produced by pulmonary artery constrictionCirc. Res.3(3)259-263(1955) 5.Kotecha, D., Calvert, M., Deeks, J.J., et al.A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trialBMJ Open7(7)e015099(2017)