Heparin stability: effects of diluent, heparin activity, container, and pH

The effects have been studied of diluent, heparin activity after dilution, container, and pH on the stability of heparin solutions stored under conditions resembling those present during heparin infusion by intravenous drip or syringe pump. Heparin activity was measured by activated partial thromboplastin time and thrombin clotting time (and, in one set of studies, also by factor Xa inhibitor assay and protamine sulphate neutralisation). Heparin activity was stable for 6 hours regardless of storage conditions. After 24 hours heparin activity was stable when the drug was diluted in 0.9% saline and stored in plastic, but a small loss of activity was observed in several studies after dilution in 5% dextrose or storage in glass. A more extensive comparison confirmed a 3-5% loss in heparin activity over 24 hours after dilution in 5% dextrose. Changing the pH to 3.5 or 10.0 had little effect on storage stability. We conclude that heparin activity in vitro remains stable during short infusions but recommend dilution in 0.9% saline and a plastic container when a heparin solution is infused over 24 hours.