title: Comparison of serum and plasma methylmalonic acid measurements in 13 laboratories: An international study.
abstract: BACKGROUND
  Detection of cobalamin deficiency is increasingly important, and methylmalonic acid (MMA) appears to be a useful marker. Information on interlaboratory variation and on methodological differences for MMA in serum and plasma is limited.
  
  
  METHODS
  Using gas chromatography/mass spectrometry, 13 laboratories participated in a 2-day analysis of 8 serum and 11 EDTA-plasma specimens. Results were analyzed for imprecision, recovery, and differences among laboratories and methods.
  
  
  RESULTS
  The mean among-laboratory imprecision (CV) was 19% and 21% for serum and plasma samples, respectively, and 9.3% and 7.8% for serum and plasma samples with added MMA, respectively. The mean within-laboratory (among-run) CV was 13% for both serum and plasma samples and 5.2% and 4.9% for serum and plasma samples with added MMA. Within-method imprecision was the same or higher than among-method imprecision. The mean among-laboratory recovery of MMA was 105% and 95% in serum and plasma, respectively. Most laboratories showed a proportional bias relative to the consensus mean of up to 15%. Two laboratories reported results that on average were almost 30% higher than the consensus mean.
  
  
  CONCLUSIONS
  No method differences were found, but significant among-laboratory imprecision was found in the present study. Improvements are needed to reduce the analytical imprecision of most laboratories, and attention must be focused on calibration issues. Differences among laboratories can be improved by introducing high-quality reference materials and by instituting external quality assessment programs.
authors.affiliation: National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA. cfp8@cdc.gov
authors.forename: C M
authors.initials: CM
authors.lastname: Pfeiffer
authors.forename: S J
authors.initials: SJ
authors.lastname: Smith
authors.forename: D T
authors.initials: DT
authors.lastname: Miller
authors.forename: E W
authors.initials: EW
authors.lastname: Gunter
mesh_terms: D002138:Calibration; D008401:Gas Chromatography-Mass Spectrometry / Q000592:standards; D006801:Humans; D007753:Laboratories / Q000592:standards*; D008764:Methylmalonic Acid / Q000097:blood* / Q000592:standards; D011786:Quality Control; D013223:Statistics as Topic; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000175:diagnosis
chemical_list: D008764:Methylmalonic Acid