RESUMO
STUDY OBJECTIVE: Intravenous N-acetylcysteine has been used as an antidote for acetaminophen poisoning for more than 25 years in Europe and Canada. In the United States, only the oral administration of N-acetylcysteine is approved by the US Food and Drug Administration. Many physicians routinely use the inhalant preparation as an intravenous formulation; however, no stability, microbiology, or pyrogen studies have been performed. In this study, we evaluate the stability and microbiology of inhalational N-acetylcysteine compounded as an intravenous formulation. METHODS: A total of 8 N-acetylcysteine solutions (solution A through H) were prepared by injecting 150 mL of 20% solution through a 22-microm filter to 1 L of 5% dextrose (D(5)W; 2.6% solution). Solutions A through C were prepared at ambient conditions (25 degrees C [77 degrees F], 65% relative humidity), and solution D was prepared at accelerated conditions (40 degrees C [104 degrees F], 75% relative humidity) for stability testing. The assays were performed by means of high-performance liquid chromatography at 0, 4, 8, 12, 24, 36, 48, 60, and 72 hours according to US Pharmacopeia XXIV methodology. Solutions E through G were assessed for bacterial growth, and solution H underwent pyrogen testing by using a Limulus amebocyte lysate method. RESULTS: Solutions A through C remained stable for at least 60 hours (<10% decomposition), but at 72 hours, there was a 10.3%, 14.9%, and 13.4% degradation, respectively. Under accelerated conditions (solution D), stability lasted for more than 72 hours. Solutions E through G remained free from bacterial growth at 72 hours, and solution H tested negative for endotoxins-pyrogens. CONCLUSION: Inhalational N-acetylcysteine prepared as an intravenous solution meets US Pharmacopeia standards for stability up to 60 hours and is free from bacteria and their byproducts, offering a viable alternative to the traditional use of oral N-acetylcysteine.
