Due to their broad spectrum of activity and wide therapeutic index, β-lactam antibiotics (β-LA) are commonly used to treat severe sepsis in critically ill patients in intensive care units. This group of patients experiences important physiological changes that alter their pharmacokinetics, and thus, therapeutic drug monitoring (TDM) of β-LA is increasingly used to improve personalized medicine by optimizing doses and minimizing the emergence of drug-resistant bacterial strains. Reliable and high-quality bioanalytical methods are needed in clinical practice. This review principally focuses on evaluating the development and validation of state-of-the-art analytical methods for the determination of β-LA in biological samples from critically ill patients. When mentioned, method optimization was performed using a univariate strategy, the currently used analytical quality by design (AQbD) tools were not used for method optimization in any study. Liquid chromatography methods coupled with UV or MS detectors were the main techniques used, and the pretreatment procedures were still considerably complex for a hospital laboratory setting. Given the poly-medication status of many patients, the selectivity of the procedure must be specifically analyzed to avoid possible interference from other drugs. However, this aspect has been assessed in very few studies. We also identified inconsistencies in analytical ranges selected in many published methods, since they are not centered in the therapeutic concentrations of the antibiotics. The precision, accuracy and linearity were mainly evaluated using diverse bioanalytical validation guidelines; however, more detailed information could have been provided about the calibration strategy used for routine laboratory assessments.
Keywords: Beta-lactam antibiotic; Bioanalytical method; Bioanalytical validation; Therapeutic drug monitoring (TDM).
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