title: Investigation of cholesterol bias due to a matrix effect of external quality assurance samples: how true is your cholesterol method?
abstract: BACKGROUND
  Comparability of cholesterol measurement is clinically required and external quality assurance (EQA) programmes are important to verify the trueness of routine methods.
  
  
  METHODS
  We developed a gas chromatography-isotope dilution mass spectrometry (GC-IDMS) total cholesterol assay to investigate the cause of a suspected matrix-related negative bias with the Beckman Coulter enzymatic method discovered in an EQA programme. The GC-IDMS method was calibrated with certified reference material and verified against a secondary reference method. Bias between the GC-IDMS and Beckman Coulter methods was estimated according to Clinical and Laboratory Standards Institute (CLSI) protocol EP9-A2 with 40 clinical samples.
  
  
  RESULTS
  At clinically important decision levels, no significant bias was demonstrated on patients' samples (all results within a ±3% limit). A matrix effect confined to the EQA material that affected the Beckman Coulter total cholesterol method was confirmed.
  
  
  CONCLUSIONS
  The GC-IDMS method is suitable as a higher order total cholesterol method in a routine clinical laboratory. Matrix effects defeat the objectives of EQA schemes by preventing the verification of trueness. Given the importance of obtaining a true cholesterol result without systematic error, we recommend that EQA material without matrix effects should be used.
authors.affiliation: Department of Chemical Pathology, Pathology Queensland, Brisbane, Block 7 Floor 3, Herston Hospitals Campus, Herston, 4029 Queensland, Australia. carel_pretorius@health.qld.gov.au
authors.forename: Carel J
authors.initials: CJ
authors.lastname: Pretorius
authors.forename: Sandra
authors.initials: S
authors.lastname: Klingberg
authors.forename: Leslie
authors.initials: L
authors.lastname: Johnson
authors.forename: Rodney
authors.initials: R
authors.lastname: Park
authors.forename: Urs
authors.initials: U
authors.lastname: Wilgen
authors.forename: Jacobus P J
authors.initials: JP
authors.lastname: Ungerer
mesh_terms: D015982:Bias; D002784:Cholesterol / Q000097:blood / Q000592:standards; D019411:Clinical Laboratory Techniques / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry / Q000592:standards*; D006801:Humans; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D002784:Cholesterol