Compatibility and osmolality of inhaled N-acetylcysteine nebulizing solution with fenoterol and ipratropium

Purpose. The compatibility, pH, and osmolality of N-acetylcysteine (NAC) nebulizing solution in the presence of ipratropium bromide or fenoterol hydrobromide were studied. Methods. Portions (400 μL) of each mixture were sampled immediately upon mixing and one, two, three, four, five, six, and seven hours after mixing and assayed by high-performance liquid chromatography. Osmolality was measured by sampling 100 μL from the filling cup at a five-minute interval during nebulization and by the freezing-point-depression method. Results. Adding NAC solution to fenoterol solution raised the pH from 3.20 to 7.90 and the osmolality to a mean ± S.D. of 1400.67 ± 4.51 mOsm/kg. Fenoterol concentrations decreased to 93.71% and NAC concentrations to 92.54% of initial concentrations after seven hours. Mixing ipratropium with NAC solution raised the pH from 3.74 to 7.95 and the osmolality to a mean ± S.D. of 1413 ± 11.79 mOsm/kg. The initial ipratropiom concentration declined 7.39% and 10.91% one and two hours after mixing with NAC solution, respectively. Conclusion. NAC and ipratropium were stable in nebulizing solution within one hour of mixing. NAC and fenoterol were compatible for at least seven hours.