Stability of stored methacholine solutions: study of hydrolysis kinetic byIP-LC

Methacholine chloride is a powerful cholinergic bronchoconstrictor agent us ed during bronchial airway hyper-responsiveness diagnosis. Methacholine: is susceptible to hydrolysis in aqueous solutions in acetic acid and S-methyl choline. In the present work, kinetics or hydrolysis with different solven ts (water and phosphate-buffered saline (PBS) pH 7.4) at different temperat ures have been studied using a newly developed high-performance liquid chro matography. At 4 degreesC, kinetic determination of hydrolysis in methachol ine chloride solutions (50 mg/ml) shows no hydrolysis in either aqueous or phosphate-buffered solutions over a 40-day period. At 30 degreesC. concentr ation of unbuffered methacholine chloride solutions remained unchanged, but buffered methacholine chloride solutions have degradation up to 5.5% over a 40-day period. At 40 degreesC, concentration of unbuffered methacholine c hloride has degradation up to 5%, and buffered methacholine chloride soluti ons have degradation up to 10% over a 40-day period. Methacholine chloride solutions are susceptibly to be used in hospital pharmacy at different conc entrations. We have studied pH and osmolality for methacholine: solutions p repared with different diluents potentially used in hospital pharmacies, i. e. deionized water, 0.9% NaCl and PBS pH 7.4. We have demonstrated that met hacholine solutions prepared with deionized water at 50 mg/ml and diluted w ith PBS pH 7.4 from 5 to 40 mg/ml are isoosmotic and potentially available for inhalation tests to measure non-specific bronchial hyper-responsiveness . (C) 2001 Elsevier Science B.V. All rights reserved.