注射用N-乙酰半胱氨酸的稳定性研究及其二聚化的化学抑制

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

作者信息

Primas Nicolas, Lano Guillaume, Brun Damien, Curti Christophe, Sallée Marion, Sampol-Manos Emmanuelle, Lamy Edouard, Bornet Charleric, Burtey Stéphane, Vanelle Patrice

机构信息

Service Central de la Qualité et de L'information Pharmaceutiques (SCQIP), Pharmacy Department, Assistance Publique-Hôpitaux de Marseille (AP-HM), 13005 Marseille, France.

CNRS, Institut de Chimie Radicalaire ICR, UMR 7273, Equipe de Pharmaco-Chimie Radicalaire, Aix-Marseille University, 13385 Marseille, France.

出版信息

Pharmaceuticals (Basel). 2023 Jan 3;16(1):72. doi: 10.3390/ph16010072.

DOI:10.3390/ph16010072

PMID:36678569

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9860916/

Abstract

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

摘要

注射用N-乙酰半胱氨酸有多种临床应用，但其使用可能因化学稳定性差而受到限制。我们成功控制了注射用N-乙酰半胱氨酸的稳定性，并研究了添加剂对N-乙酰半胱氨酸降解减少的影响。首先，验证了N-乙酰半胱氨酸及其主要降解产物二聚体的HPLC-UV定量方法，并研究了无添加剂时的稳定性。然后，评估了几种添加剂（抗坏血酸、依地酸钠、生育酚和锌）以及温度对N-乙酰半胱氨酸二聚化的影响。最后，研究了不同浓度（可用于患者）的葡萄糖酸锌的影响。当在5±3℃储存时，62.5μg·mL的葡萄糖酸锌可使25mg·mL的N-乙酰半胱氨酸溶液稳定至少8天。