title: Application of high-resolution MS for development of peptide and large-molecule drug candidates.
abstract: BACKGROUND
  For quantitative bioanalysis utilizing MS, the instrument of choice is typically a triple quadruple mass spectrometer. However, advances in high-resolution MS have allowed sensitivity and dynamic ranges to approach that of triple quadrupole instruments.
  
  
  RESULTS
  A matrix-free protein digest, a digested therapeutic protein and the intact peptide therapeutic liraglutide were each analyzed on high-resolution and triple quadrupole mass spectrometers with data compared. Samples from a mouse PK study with liraglutide were analyzed using the two different instruments, and equivalent PK exposure data were demonstrated.
  
  
  CONCLUSIONS
  High-resolution and triple quadrupole mass spectrometers can generate data resulting in identical PK parameters from an in-life sample set, thus giving confidence in either technique in support of biotherapeutic PK exposure studies.
authors.affiliation: Platform Technology & Science, Drug Metabolism & Pharmacokinetics GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Kellie
authors.affiliation: Platform Technology & Science, Drug Metabolism & Pharmacokinetics GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Kehler
authors.affiliation: Platform Technology & Science, Drug Metabolism & Pharmacokinetics GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Szapacs
mesh_terms: D000818:Animals; D005260:Female; D057230:Limit of Detection; D008297:Male; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D051379:Mice; D010455:Peptides / Q000032:analysis* / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D010455:Peptides; D004364:Pharmaceutical Preparations
keywords: assay selectivity; bioassay; cross-validation; high-resolution MS; triple-quadrupole MS