Developing a SWATH capillary LC-MS/MS method for simultaneous therapeutic drug monitoring and untargeted metabolomics analysis of neonatal plasma.

Most medications prescribed to neonatal patients are off-label uses. The pharmacokinetics and pharmacodynamics of drugs differ significantly between neonates and adults. Therefore, personalized pharmacotherapy guided by therapeutic drug monitoring (TDM) and drug response biomarkers are particularly beneficial to neonatal patients. Herein, we developed a capillary LC-MS/MS metabolomics method using a SWATH-based data-independent acquisition strategy for simultaneous targeted and untargeted metabolomics analysis of neonatal plasma samples. We applied the method to determine the global plasma metabolomics profiles and quantify the plasma concentrations of five drugs commonly used in neonatal intensive care units, including ampicillin, caffeine, fluconazole, vancomycin, and midazolam and its active metabolite α-hydroxymidazolam, in neonatal patients. The method was successfully validated and found to be suitable for the TDM of the drugs of interest. Moreover, the global metabolomics analysis revealed plasma metabolite features that could differentiate preterm and full-term neonates. This study demonstrated that the SWATH-based capillary LC-MS/MS metabolomics approach could be a powerful tool for simultaneous TDM and the discovery of neonatal plasma metabolite biomarkers.