Hydrolysis of digoxin by acid

Abstract

Abstract Predictable hydrolysis of [3H]digoxin-12α occurred in vitro with incubation in HCl or gastric juice. Hydrolysis varied with pH, time, temperature and agitation. Digoxin, the bis- and mono-digitoxosides of digoxigenin and digoxigenin were separated by silica gel thin-layer chromatography using chloroform-ethyl acetate-glacial acetic acid (25:25:1 v/v) and were quantitated by liquid scintillation spectrometry. Hydrolysis with incubation at 37° and pH 3 for 90 min was minimal, but increased with increasing acidity until >70% was hydrolysed at pH 1·2 after 30 min and >96% after 90 min incubation. At pH 0·9, 87% was hydrolysed after 30 min. In vitro hydrolysis in gastric fluid was slightly less than in HCl at the same pH. A volunteer was given 150 μCi[3H]digoxin-12α by nasogastric tube during a pentagastrin infusion when gastric pH was 0·94. He remained on his left side and samples were aspirated at intervals and immediately neutralized. Ethanol-chloroform 50:50 (v/v) extracts of the gastric fluid aspirated after 90 min and of all the urine specimens collected for 5 days were applied to a DEAE Sephadex LH-20 column. The radioactivity appeared in a single peak as digoxigenin in the 90 min gastric aspirate and in all urine specimens. Extensive intragastric hydrolysis of digoxin may occur under conditions of maximum acid output.