LC–MS/MS-based multiplex antibacterial platform for therapeutic drug monitoring in intensive care unit patients

Abstract

Empirically prescribed standard dosing regimens of antibacterial agents may result in insufficient or excess plasma concentrations with persistently poor clinical outcomes, especially for patients in intensive care units (ICUs). Therapeutic drug monitoring (TDM) of antibacterial agents can guide dose adjustments to benefit patients. In this study, we developed a robust, sensitive, and simple liquid chromatography-tandem mass spectrometry (LC–MS/MS) platform for the quantification of 14 antibacterial and antifungal agents (beta-lactams piperacillin, cefoperazone, and meropenem; beta-lactamase inhibitors tazobactam and sulbactam; antifungal agents fluconazole, caspofungin, posaconazole, and voriconazole; and daptomycin, vancomycin, teicoplanin, linezolid, and tigecycline) that can be used for patients with severe infection. This assay requires only 100 µL of serum with rapid protein precipitation. Chromatographic analysis was performed using a Waters Acquity UPLC C8 column. Three stable isotope-labeled antibacterial agents and one analogue were used as internal standards. Calibration curves ranged from 0.1–100 μg/mL, 0.1–50 μg/mL, and 0.3–100 μg/mL for different drugs, and all correlation coefficients were greater than 0.9085. Intra- and inter-day imprecision and inaccuracy values were below 15%. After validation, this new method was successfully employed for TDM in routine practice.

Simultaneous Quantification of Seven Antifungal Agents in Human Serum Using Liquid Chromatography-Tandem Mass Spectrometry

“…The parent and product ions used in these analyses are listed in Table 1. For quantification and confirmation, two distinct m/z transitions were selected for each analyte [25]. All analytes were detected in the positive mode of electrospray ionization (ESI), except for micafungin and ethylparaben (used as the internal standard for micafungin), which exhibited insufficient intense ion fragmentation in this mode.…”

Determination of vancomycin and meropenem in serum and synovial fluid of patients with prosthetic joint infections using UPLC–MS/MS

“…18,24,25 The determination methods for MEM were mainly performed by LC methods. 18 Although various analytical methods, mainly for liquid chromatography-tandem mass spectrometry (LC-MS/MS) [26][27][28][29][30][31][32][33] and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) [34][35][36][37][38] have been reported for simultaneous determination of VAN, MEM and other antibiotics in plasma and serum. There are only a few studies reporting the analysis of VAN, MEM in synovial fluid.…”

Outcome of hospital-acquired bloodstream infection: interplay between bacteria, host, and healthcare system organization

“…Indeed, this study highlights a number of factors supporting this possibility, Including what can be seen as complementary measures to ensuring optimal antibiotic dosing, i.e., good access to TDM and good availability of clinical pharmacists. Although beta-lactams, vancomycin, and aminoglycoside levels are now routinely monitored in many institutions, TDM of almost all other antibiotics is about to be part of routine care [7]. It is increasingly recognized that personalized antibiotic dosing in critically ill patients is associated with better outcomes, especially in the early phase of sepsis [8].…”