Digoxin - a therapeutic agent and mechanistic probe: review of liquid chromatographic mass spectrometric methods and recent nuances in the clinical pharmacology attributes of digoxin.

Digoxin is an important therapeutic agent for the treatment of congestive cardiac failure. In spite of its narrow therapeutic index, digoxin has been used extensively by the medical community and, lately, the use of digoxin as a mechanistic probe for p-glycoprotein transporter activity has increased. This review describes recent trends in the bioanalysis of digoxin, where scores of liquid chromatographic-mass spectrometric assays have been successfully employed to measure digoxin in preclinical, clinical and mechanistic studies. It provides various considerations such as internal standard selection, extraction schemes, matrix effect, selectivity evaluation and optimization of mass spectral conditions, for example, to enable the development of sound bioanalytical methods for digoxin. Some recent updates with regard to clinical pharmacology, absorption and disposition aspects of digoxin have been included. Overall, liquid chromatographic-mass spectrometric assays represent an important tool for many future preclinical, clinical and mechanistic probe studies that would probe digoxin with or without other coadministered substrates.