Stability Study of Parenteral N-Acetylcysteine, and Chemical Inhibition of Its Dimerization

Parenteral N-acetylcysteine has a wide variety of clinical applications, but its use can be limited by a poor chemical stability. We managed to control parenteral N-acetylcysteine stability, and to study the influence of additives on the decrease of N-acetylcysteine degradation. First, an HPLC-UV dosing method of N-acetylcysteine and its main degradation product, a dimer, was validated and the stability without additive was studied. Then, the influence of several additives (ascorbic acid, sodium edetate, tocopherol and zinc) and of temperature on N-acetylcysteine dimerization was evaluated. Finally, the influence of zinc gluconate at different concentrations (administrable to patients) was investigated. Zinc gluconate at 62.5 mu g center dot mL(-1) allows the stabilization of 25 mg center dot mL(-1) N-acetylcysteine solution for at least 8 days when stored at 5 +/- 3 degrees C.

Automated summary

By studying the influence of additives on the degradation of N-acetylcysteine, it was found that the addition of zinc gluconate at a certain concentration can stabilize the solution and extend its shelf life.