Introduction. N-acetylcysteine (NAC) is the antidote for acetaminophen (Tylenol) toxicity from over ingestion leading to 56,000 emergency room visits yearly. This is worrisome due to the risk of hepatoxicity, especially in children and adolescents. Often, nausea and vomiting are associated with NAC use and is treated acutely by ondansetron (Zofran), a 5-HT3 receptor antagonist. Inconveniently, the NAC 21-hour intravenous (IV) infusion needs to be halted with IV flushing before ondansetron can be administered. Another IV flushing follows before NAC is resumed. This causes treatment interruption in a medical emergency; therefore, we are investigating the IV compatibility of NAC and ondansetron to reduce the steps in treating acute nausea/vomiting.
Methods. A reverse phase high-performance liquid chromatography (RP-HPLC) method was utilized for NAC quantification. The analysis was conducted on an Agilent Eclpise XDB-C18 column (3.5 micron, 4.6 x 150 mm) with a mobile phase containing acetonitrile (ACN), water (10:90 v/v), and 0.1 % trifluoroacetic acid (TFA). The flow rate was set at 0.500 mL/min with an injection volume of 10 microliters and a temperature of 50oC. A UV wavelength of 212 nm was utilized for detection of NAC. A liquid chromatography mass spectrometry (LC – MS/MS) method was able to quantify levels of ondansetron. A Waters XBridge C18 column (3.5 micron, 4.6 x 150 mm) was used for separation of ondansetron. The mobile phase included ammonium formate buffer (pH 3.0, 5 mM) and acetonitrile (15:85, v/v) with the flow rate set at 0.500 mL/min. Electrospray ionization interface is set in the positive mode for measurement of ondansetron using a precursor ion of m/z 294.0200.
Results. The HPLC-UV and LC-MS/MS methods for NAC and ondansetron, respectively, will be validated for linearity, precision and accuracy. Then the methods will be applied toward a chemical compatibility investigation of NAC and ondansetron through medical grade tubing and y-site. The ideal outcome would be to confidently assume NAC and ondansetron are IV compatible for y-site administration to avoid infusion interruption for treatment of acetaminophen toxicity.
Conclusion. IV compatibility for NAC and ondansetron affords no infusion interruptions reducing unnecessary risk of acetaminophen toxicity. This also decreases risk of medical errors based on the multi-step process to administer ondansetron with receiving NAC. Overall, compatibility could create safer, more efficient protocols for treatment of acute nausea/vomiting from NAC administration
