A UHPLC–MS/MS method for the simultaneous determination of piperacillin and tazobactam in plasma (total and unbound), urine and renal replacement therapy effluent

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Graphical abstractHighlightsSimultaneous measurement of piperacillin-tazobactam using UHPLC–MS/MS.Validated for a range of clinically-relevant matrices.Application of microsample volumes for analysis of plasma (total), urine and RRTE.Method applied to a clinical pharmacokinetic study of a critically ill patient.Piperacillin-tazobactam is a beta-lactam/beta-lactamase combination antibiotic used in patients with moderate to severe infection. Dosing of piperacillin-tazobactam requires an understanding of this patient group to maximise the effectiveness of this antibiotic and limit a further emergence of resistant pathogens. This is the first method that measures piperacillin and tazobactam simultaneously, across this range of clinically-relevant biological matrices. The calibration line was linear across the concentration range of 0.5–500 μg/mL for piperacillin and 0.625–62.5 μg/mL for tazobactam. All validation testing for matrix effects, precision and accuracy, specificity and stability were within 15%. A calibration equivalence study was performed to investigate the suitability of applying calibration curves prepared in an alternative matrix, with a mean bias of −10.8% identified for the application of a calibration line prepared for tazobactam in plasma only. Bias for all other calibration lines prepared in alternate matrices was within the 5% acceptance criteria. The method was successfully applied to a pharmacokinetic study of a critically ill patient receiving renal replacement therapy, with the results included.

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