title: Determination of avibactam and ceftazidime in human plasma samples by LC-MS.
abstract: OBJECTIVE
  Avibactam, a novel non-β-lactam β-lactamase inhibitor co-administrated with the β-lactam antibiotic ceftazidime, is in clinical development. The need to evaluate its PK and PD requires accurate and reliable bioanalytical methods.
  
  
  METHODS
  We describe LC-MS/MS methods for the determination of avibactam and ceftazidime in human plasma. Avibactam was extracted using weak anionic exchange solid-phase extraction and analyzed on an amide column. Ceftazidime was extracted using protein precipitation and analyzed on a C18 column. Calibration curves were established over 10-10,000 ng/ml (avibactam) and 43.8-87,000 ng/ml (ceftazidime).
  
  
  CONCLUSIONS
  Method validation, cross-validation between three laboratories and incurred sample re-analysis demonstrated method robustness. The methods were successfully applied to multiple clinical studies.
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Sillén
authors.affiliation: Covance, Harrogate, HG3 1PY, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Mitchell
authors.affiliation: LGC, Fordham, Cambridgeshire, CB7 5WW, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sleigh
authors.affiliation: AstraZeneca, Macclesfield, Cheshire East SK10 2NA, UK.
authors.forename: Guy
authors.initials: G
authors.lastname: Mainwaring
authors.affiliation: Covance, Harrogate, HG3 1PY, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Catton
authors.affiliation: Quotient Bioresearch, Rushden, Northamptonshire, NN10 6ER, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Houghton
authors.affiliation: AstraZeneca, Macclesfield, Cheshire East SK10 2NA, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Glendining
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000592:standards; D053961:Azabicyclo Compounds / Q000097:blood* / Q000737:chemistry / Q000592:standards; D001774:Blood Chemical Analysis / Q000379:methods*; D002442:Ceftazidime / Q000097:blood* / Q000737:chemistry / Q000592:standards; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D011786:Quality Control; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; C543519:avibactam; D002442:Ceftazidime