Journal article
Development and validation of a simple and sensitive LC-MS/MS method for the quantification of cefazolin in human plasma and its application to a clinical pharmacokinetic study
Journal of pharmaceutical and biomedical analysis, Vol.210, pp.114521-114521
02/20/2022
DOI: 10.1016/j.jpba.2021.114521
PMID: 34979494
Abstract
•A sensitive, robust and high throughput LC-MS/MS method of cefazolin in human plasma was established.•Full validations conducted under the GLP environment, with 17 validation parameters all passed the FDA criteria.•The developed LC-MS/MS method of cefazolin was successfully applied to a clinical pharmacokinetic study.
Cefazolin is widely used during surgery to prevent surgical site infections (SSIs). Although cefazolin redosing is often needed due to its short half-life, the appropriate redosing schedule remains controversial and there is limited information on cefazolin disposition following repeated doses during surgery. In parallel with an ongoing cefazolin redosing clinical study, we have developed and fully validated a simple and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of cefazolin in human plasma. A simple protein precipitation was used for sample preparation. MS/MS analysis was performed using multiple reaction monitoring (MRM) under a positive ionization mode. The lower limit of quantification (LLOQ) for cefazolin was evaluated at 0.25 µg/mL and a linearity ranging from 0.25 to 300 µg/mL. Accuracy was ≤ 114.3% for quality controls and ≤ 118.2% for LLOQ; intra-day and inter-day precision ranging from 1.9% to 14.2% for all quality controls and LLOQ. Matrix effect, extraction recovery, stability testing, dilution integrity, hemolysis effects and whole blood stability have all been investigated. A total of 17 parameters were validated and passed their validation criteria. The method was applied in the quantification of cefazolin in clinical plasma samples and was able to successfully determine the concentrations in patients undergoing various surgeries. In comparison with other prior published methods, our method has a simple sample preparation combined with a short analysis run time, a wide dynamic range and low limit of quantification, and is a fully validated assay that abides by FDA guidance.
Details
- Title: Subtitle
- Development and validation of a simple and sensitive LC-MS/MS method for the quantification of cefazolin in human plasma and its application to a clinical pharmacokinetic study
- Creators
- Joshua A. Reeder - University of IowaInas A. Abdallah - University of IowaThanh Bach - University of IowaCormac T. O’Sullivan - College of Nursing, University of Iowa Hospital and Clinics, USAYan Xu - University of IowaDemet Nalbant - University of IowaGuohua An - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of pharmaceutical and biomedical analysis, Vol.210, pp.114521-114521
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.jpba.2021.114521
- PMID
- 34979494
- ISSN
- 0731-7085
- eISSN
- 1873-264X
- Language
- English
- Date published
- 02/20/2022
- Academic Unit
- Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Nursing; Pharmaceutics
- Record Identifier
- 9984366027202771
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