title: Optimized LC-MS/MS quantification method for the detection of piperacillin and application to the development of charged liposaccharides as oral penetration enhancers.
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.
authors.affiliation: School of Molecular and Microbial Sciences, The University of Queensland, Brisbane, Australia.
authors.forename: Aude
authors.initials: A
authors.lastname: Violette
authors.forename: Diego A Faria
authors.initials: DA
authors.lastname: Cortes
authors.forename: Julie A
authors.initials: JA
authors.lastname: Bergeon
authors.forename: Robert A
authors.initials: RA
authors.lastname: Falconer
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
mesh_terms: D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018938:Caco-2 Cells; D002853:Chromatography, Liquid / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry; D010539:Permeability; D010878:Piperacillin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D005079:Excipients; D008070:Lipopolysaccharides; D010878:Piperacillin