Stability of <i>N</i>-Acetylcysteine (NAC) in Standardized Pediatric Parenteral Nutrition and Evaluation of <i>N</i>,<i>N</i>-Diacetylcystine (DAC) Formation

• Main Authors: Isabelle Sommer, Hervé Schwebel, Vincent Adamo, Pascal Bonnabry, Lucie Bouchoud, Farshid Sadeghipour
• Format: Article
• Language: English
• Published: MDPI AG 2020-06-01
• Series: Nutrients
• Subjects: parenteral nutrition; pediatrics; amino acids; cysteine; <i>N</i>-acetylcysteine; <i>N</i>,<i>N</i>-diacetylcystine
• Online Access: https://www.mdpi.com/2072-6643/12/6/1849

The ESPGHAN/ESPEN/ESPR-Guidelines on pediatric parenteral nutrition (PPN) recommend the administration of the semiessential amino acid (AA) cysteine to preterm neonates due to their biochemical immaturity resulting in an inability to sufficiently synthetize endogenous cysteine. The soluble precursor <i>N</i>-acetylcysteine (NAC) is easily converted into bioavailable cysteine. Its dimer <i>N</i>,<i>N</i>-diacetylcystine (DAC) is almost unconvertable to cysteine when given intravenously resulting in a diminished bioavailability of cysteine. This study aims to understand the triggers and oxidation process of NAC to DAC to evaluate possibilities of reducing DAC formation in standardized PPN. Therefore, different air volumes (21% O₂) were injected into the AA compartment of a standardized dual-chamber PPN. O₂ concentrations were measured in the AA solution and the headspaces of the primary and secondary packaging. NAC and DAC concentrations were analyzed simultaneously. The analysis showed that O₂ is principally delivered from the primary headspace. NAC oxidation exclusively delivers DAC, depending on the O₂ amount in the solution and the headspaces. The reaction of NAC to DAC being containable by limiting the O₂ concentration, the primary headspace must be minimized during manufacturing, and oxygen absorbers must be added into the secondary packaging for a long-term storage of semipermeable containers.