FORMATION OF [20R]-DIHYDRODIGOXIN FROM DIGOXIN IN HUMANS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 13  (1) , 51-57
Abstract
The stereochemical identity of dihydrodigoxin (DHD3), a metabolite of digoxin excreted in urine after digoxin administration in man was determined. Separation of the individual epimers in reference DHD3 was affected by a chemical derivatization-HPLC [high performance liquid chromatography] procedure. Comparison of individual derivatized epimers of DHD3 with the known 20R and 20S epimers of derivatized dihydrodigoxigenin using chromatographic data and NMR spectroscopy permitted identification of the 20R and 20S epimers in reference DHD3. Material corresponding chromatographically to R-DHD3 was isolated from urine of a volunteer taking oral digoxin daily. The NMR spectrum of the chromatographically pure, derivatized urinary isolate was identical to the NMR spectrum of derivatized R-DHD3. Urine samples from 20 patients on chronic digoxin therapy and from 2 volunteers were surveyed for chromatographic evidence of R- or S-DHD3 using HPLC of a fluorescent derivative as well as HPLC of a UV-absorbing derivative. The more sensitive fluorescence procedure yielded evidence for R-DHD3 in 8 patients and both volunteers. There was a sufficient concentration in 4 patients and both volunteers for independent evidence of R-DHD3 using the UV-absorbing derivatives. Chromatographic evidence (fluorescent derivative) for S-DHD3 was found in urine from 3 patients. This evidence for S-DHD3 was demonstrated to be an artifact by the absence of the peak expected for S-DHD3 in the chromatogram of the UV-absorbing derivative as well as by the inability of fecal incubates to convert digoxin to S-DHD3. The DHD3 metabolite formed in humans is evidently the 20R epimer.

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