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

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 16; no. 1
• Main Authors: Primas, Nicolas, Lano, Guillaume, Brun, Damien, Curti, Christophe, Sallée, Marion, Sampol-Manos, Emmanuelle, Lamy, Edouard, Bornet, Charleric, Burtey, Stéphane, Vanelle, Patrice
• Format: Journal Article
• Language: English
• Published: MDPI 03.01.2023
• Subjects: Life Sciences; parenteral administration; stability study; N-acetylcysteine stability study parenteral administration; N-acetylcysteine
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph16010072

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 µg·mL−1 allows the stabilization of 25 mg·mL−1 N-acetylcysteine solution for at least 8 days when stored at 5 ± 3 °C.