title: Direct comparison of radioimmunoassay and LC-MS/MS for PK assessment of insulin glargine in clinical development.
abstract: BACKGROUND
  A direct comparison of radioimmunoassay (RIA) and LC-MS/MS for insulin glargine quantification in human plasma is provided.
  
  
  RESULTS
  Compared with the RIA, the LC-MS/MS assay exhibited comparable/improved sensitivity (LLOQ at 0.1 ng/ml [˜16.7 pM or 2.8 μU/ml] for glargine and its metabolites M1 and M2, respectively) and ruggedness. Most importantly, it demonstrated a superior specificity advantage against the interference from endogenous insulin, exogenous insulin analogs (e.g., Novolog(®), Humalog(®) or Levemir(®), routine treatment for diabetes mellitus) and potentially pre-existing anti-insulin antibodies in patient samples. The data obtained from diabetic patients suggested the LC-MS/MS assay substantially improved pharmacokinetic characterization of glargine.
  
  
  CONCLUSIONS
  LC-MS/MS overcame common limitations of RIA, and provided critically needed specificity to support glargine clinical development, without sacrificing assay sensitivity and ruggedness.
authors.affiliation: Regulated Bioanalysis, PPDM, 770 Sumneytown Pike, WP75B-300, West Point, PA 19486, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Marita
authors.initials: M
authors.lastname: Prohn
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Cai
authors.forename: Michael
authors.initials: M
authors.lastname: Crutchlow
authors.forename: Sudha S
authors.initials: SS
authors.lastname: Shankar
authors.forename: Kevin
authors.initials: K
authors.lastname: Bateman
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Woolf
mesh_terms: D000595:Amino Acid Sequence; D016477:Artifacts; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D002853:Chromatography, Liquid; D055808:Drug Discovery; D006801:Humans; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000097:blood* / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics*; D008969:Molecular Sequence Data; D011863:Radioimmunoassay / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D001323:Autoantibodies; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine