Hydrolysis of digoxin by acid.

Predictable hydrolysis of [3H]digoxin-12alpha 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 degrees and pH 3 for 90 min was minimal, but increased with increasing acidity until greater than 70% was hydrolysed at pH 1-2 after 30 min and greater than 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 muCi[3H]digoxin-12alpha 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.

The effect on serum ionic magnesium of exchange transfusion with citrated as opposed to heparinized blood.

Serum Mg++ levels before, during, and after replacement transfusion were determined in 20 newborn infants. In 10 infants exchanged with acid-citrate-dextrose (ACD) blood, the level fell from 1.75 +/- 0.16 mEq./l. to 0.99 +/- 0.16 mEq./l. By contrast, levels in 10 infants exchanged with two types of heparinized blood were unchanged: the pre-exchange values were 1.59 +/- 0.11, and the postexchange levels were 1.59 +/- 0.08 mEq./l. Mean values for donor bloods were 0.42 +/- 0.07 mEq./l. with ACD blood, and 1.45 +/- 0.03 mEq./l. with heparinized blood. In vitro studies involving the addition of known amounts of citrate to standard Mg++ solutions demonstrated that the citrate caused a reduction of ionic magnesium. It is proposed that the fall in serum Mg++ when ACD blood is used for exchange transfusion is the combined result of Mg++ binding by the citrate, and the dilution effect of the relatively large proportion of anticoagulant to blood (1:3) used with the ACD mixture.