The Identification and Measurement in Urine of Dihydrodigoxin, a Cardioinactive Metabolite of Digoxin

Summary

The sensitivity of an established mass spectroscopic technique has been improved in order to measure dihydrodigoxin, the cardioinactive metabolite of digoxin, in extracts of urine from paediatric patients maintained on the drug.

Aliquots were vapourized in a reproducible manner and the ion current at m/e 355.227 and 339.232 (characteristic of digoxin and dihydrodigoxin respectively) monitored at a resolving power of 5,000 throughout the evaporation process. The integrated ion current at each ion mass was proportional to the amount of each steroid admitted. The technique was validated by examining urine extracts containing known amounts of digoxin and dihydrodigoxin. Less than 0.01% of digoxin was converted to dihydrodigoxin during the extraction process.

The percentage of the daily maintenance dose excreted in urine in 24 h as this metabolite was low (mean 4.35%) compared to adults (mean 16.4%), with a wide variation between subjects. There was no significant difference between the results from subjects under one year of age and those over one year. Thus metabolism of digoxin to dihydrodigoxin does not appear to account for the increased dosage requirement of paediatric patients.