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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
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An adapted LC-MS/MS method for the determination of free plasma concentration of cefoperazone in children:

Min Kan1, Yue-E Wu1, Xue Li1

  • 1Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
|April 5, 2020
PubMed

Insights

Determining free cefoperazone levels in children is crucial for effective treatment. This study developed a validated LC-MS/MS method using minimal plasma, revealing significant individual variability in unbound drug concentrations.

Area of Science:

  • Pharmacokinetics
  • Analytical Chemistry
  • Pediatric Pharmacology

Background:

  • Cefoperazone's antimicrobial activity relies on its unbound concentration.
  • Limited protein binding data in children hinders optimal pediatric therapy.
  • Lack of validated methods for free cefoperazone in small pediatric samples.

Purpose of the Study:

  • Develop and validate an LC-MS/MS method for free cefoperazone determination in pediatric plasma.
  • Address the challenge of limited sample volumes in pediatric pharmacokinetic studies.
  • Provide a tool for optimizing cefoperazone dosing in children.

Main Methods:

  • Developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.
  • Utilized ultrafiltration with only 70 μL of plasma.
  • Employed a C18 column and gradient elution with acetonitrile/water mobile phase.
  • Detected cefoperazone and ceftiofur (internal standard) using negative electrospray ionization.

Main Results:

  • Achieved excellent linearity (5-5000 ng/mL) and high accuracy (91.5-105.0%).
  • Demonstrated excellent precision (CV < 9.0%), low matrix effect (< 11.7%), and high recovery (92.9-95.9%).
  • Successfully applied the method to pediatric patients, showing significant individual variability in unbound cefoperazone (8.1-48.0%).

Conclusions:

  • The validated LC-MS/MS method is suitable for determining free cefoperazone in pediatric plasma.
  • Age and albumin levels significantly influence cefoperazone protein binding in children.
  • This method facilitates personalized antimicrobial therapy optimization in pediatric patients.

Keywords:
CefoperazoneChildrenFree concentrationLC-MS/MSProtein binding

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