title: The measurement of a fibrinogen α C-chain 5.9 kDa fragment (FIC 5.9) using MALDI-TOF MS and a stable isotope-labeled peptide standard dilution.
abstract: BACKGROUND
  We previously identified a 5.9 kDa peptide fragment of fibrinogen α C-chain (FIC 5.9) as a novel biomarker candidate for heavy drinking. In an effort to improve FIC 5.9 measurement for potential use in clinical diagnostics, we combined the ClinProt System and a stable isotope-labeled peptide standard dilution as a simple and reproducible system for measuring FIC 5.9.
  
  
  METHODS
  We analyzed 104 serum samples that were obtained from patients with alcohol dependency, from patients with chronic hepatitis C, and from healthy volunteers. Serum FIC 5.9 levels were measured using the ClinProt system with and without a stable isotope-labeled synthetic FIC 5.9 as an internal standard.
  
  
  RESULTS
  The within-day and between-day CVs were significantly smaller with stable isotope dilution mass spectrometry (SID-MS) than with conventional MALDI-TOF MS. Of the two different MALDI-TOF MS platforms, we obtained concordant results with SID-MS. Furthermore, only SID-MS detected a small but significant difference between the serum FIC 5.9 levels in the chronic hepatitis C group and the controls.
  
  
  CONCLUSIONS
  MALDI-TOF MS with a stable isotope-labeled peptide spike can determine serum FIC 5.9 levels more precisely than conventional MS. This will make inter-laboratory FIC 5.9 comparisons possible.
authors.affiliation: Clinical Proteomics Research Center, Chiba University Hospital, Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sogawa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kodera
authors.forename: Kenta
authors.initials: K
authors.lastname: Noda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ishizuka
authors.forename: Mako
authors.initials: M
authors.lastname: Yamada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Umemura
authors.forename: Katsuya
authors.initials: K
authors.lastname: Maruyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomonaga
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
authors.forename: Fumio
authors.initials: F
authors.lastname: Nomura
mesh_terms: D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000097:blood; D001774:Blood Chemical Analysis / Q000379:methods*; D005340:Fibrinogen / Q000737:chemistry*; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D010446:Peptide Fragments / Q000097:blood* / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D055815:Young Adult
chemical_list: D010446:Peptide Fragments; C098000:fibrinogen alphaC; D005340:Fibrinogen