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

Abstract
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 0.5-500μg/mL for piperacillin and 0.625-62.5μg/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.
AuthorsSaiyuri Naicker, Yarmarly C Guerra Valero, Jenny L Ordenez Meija, Jeffrey Lipman, Jason A Roberts, Steven C Wallis, Suzanne L Parker
JournalJournal of pharmaceutical and biomedical analysis (J Pharm Biomed Anal) Vol. 148 Pg. 324-333 (Jan 30 2018) ISSN: 1873-264X [Electronic] England
PMID29080413 (Publication Type: Journal Article)
CopyrightCopyright © 2017 Elsevier B.V. All rights reserved.
Chemical References
  • Piperacillin, Tazobactam Drug Combination
  • Penicillanic Acid
  • Tazobactam
  • Piperacillin
Topics
  • Calibration
  • Chromatography, High Pressure Liquid
  • Critical Illness
  • Humans
  • Penicillanic Acid (analogs & derivatives, blood, urine)
  • Piperacillin (blood, urine)
  • Piperacillin, Tazobactam Drug Combination
  • Plasma (chemistry)
  • Renal Replacement Therapy (methods)
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry (methods)
  • Tazobactam
  • Urine (chemistry)

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