Stability of five catecholamines and terbutaline sulfate in 5% dextrose injection in the absence and presence of aminophylline.

The stability of dopamine hydrochloride, epinephrine hydrochloride, isoproterenol hydrochloride, methyldopate hydrochloride, norepinephrine bitartrate, and terbutaline sulfate in 5% dextrose injection with and without aminophylline was evaluated. Kinetic data were obtained from the stability-indicating, high-performance liquid chromatographic assay method for autoxidation of the five sympathomimetic catecholamines and terbutaline sulfate. The autoxidation of epinephrine hydrochloride, isoproterenol hydrochloride, norepinephrine, bitartrate, and terbutaline sulfate was much faster in the alkaline solutions (pH 7.7-8.1) containing aminophylline than in the acidic solutions (pH 3.9-4.5) without aminophylline. On a molar basis among beta 2 agonists, terbutaline sulfate was considerably more stable than epinephrine hydrochloride or isoproterenol hydrochloride. The autoxidation of terbutaline sulfate and the five catecholamines followed apparent zero-order kinetics. The rate constants and degradation times to fall 90% of original potency were determined for each drug. Visual inspection was found to be grossly inadequate for estimating the stability of catecholamines to autoxidation. Epinephrine hydrochloride, norepinephrine bitartrate, and isoproterenol hydrochloride should not be combined with aminophylline or similarly alkaline drugs in LVP solutions. The stability of very potent and life-saving drugs prepared for i.v. admixtures must be studied with stability-indicating assay methods.