Therapeutic drug monitoring of piperacillin: Agreement between quantitative nuclear magnetic resonance spectroscopy and liquid chromatography with tandem mass spectrometry

In clinical practice, therapeutic drug monitoring (TDM) typically relies on specialized immunoassays or chromatography-based methods. These approaches require drug-specific setups and are limited to batch measurements, which can restrict their availability. Recent advances in quantitative nuclear magnetic resonance spectroscopy (qNMR) have made it suitable for rapid and reliable quantification of small molecules in human plasma. However, no qNMR-based method has yet been developed specifically for TDM. A qNMR method for quantification of PIP in human plasma was developed. Plasma samples were collected from 15 patients receiving PIP treatment in an intensive care unit. A total of 126 samples were subjected to analysis using 1 H-NMR spectroscopy and isotope dilution liquid chromatography–tandem mass spectrometry. Measurements were compared within the common quantifiable range of 10 to 100 mg/L. The degree of agreement between the methods was assessed using linear regression with post-hoc bootstrapping and Bland–Altman analysis. The concordance correlation coefficient between methods was 0.895, suggesting good alignment. Linear regression showed agreement with an intercept of –0.50 mg/L and a slope of 1.03. Bland–Altman analysis revealed a mean bias of –0.85 mg/L, with limits of agreement from –18.67 mg/L to +16.97 mg/L. This study demonstrates the potential of qNMR as a viable alternative for therapeutic drug monitoring, with a promising level of agreement supporting further validation in larger patient cohorts. • A novel quantitative nuclear magnetic resonance spectroscopy method was developed for quantifying piperacillin in plasma for therapeutic drug monitoring in intensive care patients. • Quantitative nuclear magnetic resonance spectroscopy is sample-sparing, allows random-access analysis, and has rapid turn-around times. • Quantitative nuclear magnetic resonance spectroscopy reliably quantified piperacillin within the clinically relevant therapeutic range of 10 to 100 mg/L. • Quantitative nuclear magnetic resonance spectroscopy shows promise as an alternative for TDM of antibiotics in critically ill patients.