Stability of methacholine chloride in bronchial provocation test solutions

The stability of methacholine chloride (5 mg/ml) in 0.9% sodium chloride solution was measured. A reliable colorimetric assay (530 nm) based on the formation of a hydroxamic acid-iron complex was used. At appropriate time intervals, samples were removed from solutions stored at 4, 20, 37, 60, or 80 degrees C and assayed. The degradation of methacholine chloride followed apparent first-order kinetics of methacholine chloride followed apparent first-order kinetics at all temperatures, with observed half-lives ranging from 29.3 days at 80 degrees C to 693 days 4 degrees C. Methacholine chloride in 0.9% sodium chloride solution does not degrade as rapidly as previously suggested. According to an Arrhenius plot, storage of such solutions at 30 or 4 degrees C would result in not more than 10% degradation over a period of approximately two or five months, respectively. Thus, it should be possible to prepare stock solutions of this deliquescent drug.