Optimized LC-MS/MS quantification method for the detection of piperacillin and application to the development of
Aude Violette1, Diego A Faria Cortes, Julie A Bergeon
1School of Molecular and Microbial Sciences, The University of Queensland, Brisbane, Australia.
Abstract:
Piperacillin, a potent beta-lactam antibiotic, is effective in a large variety of Gram+ and Gram- bacterial infections but its administration is limited to the parenteral route as it is not absorbed when given orally. In an attempt to overcome this problem, we have synthesized a novel series of charged liposaccharide complexes of piperacillin comprising a sugar moiety derived from d-glucose conjugated to a lipoamino acid residue with varying side-chain length (cationic entity) and the piperacillin anion. A complete multiple reaction monitoring LC-MS/MS method was developed to detect and characterize the synthesized complexes. The same method was then successfully applied to assess the in vitro apparent permeability values of the charged liposaccharide complexes in Caco-2 monolayers.
Insights
Researchers developed novel charged liposaccharide complexes of piperacillin to enable oral administration. These complexes showed promising in vitro apparent permeability, potentially overcoming limitations of parenteral antibiotic delivery.
Area of Science:
- Pharmaceutical Chemistry
- Drug Delivery Systems
- Microbiology
Background:
- Piperacillin is a beta-lactam antibiotic effective against Gram-positive and Gram-negative bacteria.
- Current administration of piperacillin is restricted to parenteral routes due to poor oral absorption.
- Oral bioavailability of antibiotics is a significant challenge in infectious disease treatment.
Purpose of the Study:
- To synthesize novel charged liposaccharide complexes of piperacillin for potential oral administration.
- To develop and validate a sensitive analytical method for characterizing these novel complexes.
- To evaluate the in vitro permeability of the synthesized piperacillin complexes.
Main Methods:
- Synthesis of charged liposaccharide complexes using d-glucose, lipoamino acids, and piperacillin.
- Development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with multiple reaction monitoring (MRM).
- Assessment of in vitro apparent permeability using Caco-2 cell monolayers.
Main Results:
- Successful synthesis of a novel series of charged liposaccharide complexes of piperacillin.
- A robust LC-MS/MS method was established for the detection and characterization of the complexes.
- The synthesized complexes demonstrated measurable in vitro apparent permeability in Caco-2 cell models.
Conclusions:
- Novel charged liposaccharide complexes of piperacillin have been successfully synthesized.
- The developed LC-MS/MS method is suitable for analyzing these complex drug formulations.
- These findings suggest a potential strategy for developing orally bioavailable piperacillin formulations.
