Journal article
Development and validation of a simple and sensitive LC-MS/MS method for quantification of ampicillin and sulbactam in human plasma and its application to a clinical pharmacokinetic study
Journal of pharmaceutical and biomedical analysis, Vol.196, pp.113899-113899
03/20/2021
DOI: 10.1016/j.jpba.2021.113899
PMID: 33508765
Abstract
•A sensitive, fast and robust LC–MS/MS method of ampicillin and sulbactam in human plasma was established.•Full validations conducted under the GLP environment, with 16 validation parameters all passed the FDA criteria.•The developed LC–MS/MS method of ampicillin and sulbactam was successfully applied to a clinical pharmacokinetic study.
Ampicillin-sulbactam is a broad-spectrum combination antibiotic used for a variety of clinical applications, including as a prophylactic agent to reduce the risk of surgical site infection. The pharmacokinetics of ampicillin-sulbactam after redosing during prolonged surgeries remains incompletely understood. In anticipation of further studying the intra-operative pharmacokinetics of this drug, we have developed a novel liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for the quantification of ampicillin and sulbactam. The plasma samples were prepared using a simple protein precipitation method. Gradient chromatographic elution was used to separate analytes, and MS/MS analysis was performed in negative ionization mode for both analytes via multiple reaction monitoring (MRM). All validation parameters were evaluated under a good laboratory practice (GLP) environment. For both ampicillin and sulbactam, the lower limit of quantitation (LLOQ) was established as 0.25 μg/mL. The calibration curve ranged from 0.25 to 200 μg/mL for ampicillin and 0.25–100 μg/mL for sulbactam. Inter- and intra-day precisions for both analytes were ≤11.5 % for quality controls and ≤17.4 % for LLOQ; accuracies ranged from -11.5 to 12.5% for 3 quality control levels and -18.1–18.7% for LLOQ. In addition to sensitivity, accuracy and precision, 13 other parameters were also validated for both analytes, and the results met the acceptance criteria. Our method was successfully applied to quantify ampicillin and sulbactam concentrations in patients undergoing surgery.
Details
- Title: Subtitle
- Development and validation of a simple and sensitive LC-MS/MS method for quantification of ampicillin and sulbactam in human plasma and its application to a clinical pharmacokinetic study
- Creators
- Demet Nalbant - University of IowaJoshua A. Reeder - University of IowaPeizhi Li - University of IowaCormac T. O’Sullivan - College of Nursing, University of Iowa Hospital and Clinics, USAWilliam K. Rogers - University of Minnesota Medical SchoolGuohua An - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of pharmaceutical and biomedical analysis, Vol.196, pp.113899-113899
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.jpba.2021.113899
- PMID
- 33508765
- ISSN
- 0731-7085
- eISSN
- 1873-264X
- Language
- English
- Date published
- 03/20/2021
- Academic Unit
- Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Nursing; Anesthesia
- Record Identifier
- 9984365902402771
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