title: A liquid chromatography-tandem mass spectrometry method for the determination of nodularin-R in human plasma and its preliminary clinical application.
abstract: BACKGROUND
  Nodularins are an important class of hepatotoxic cyclic pentapeptides that most current methods are ill-suited to clinically monitor. Therefore, a liquid chromatography-tandem mass spectrometry (LC/MS/MS) assay for the determination of nodularin-R in human plasma was validated and applied to clinical samples in this report.
  
  
  METHODS
  Sample cleanup and enrichment were achieved using solid phase extraction. The concentration of nodularin-R in each sample was calculated using the relative abundance area ratio of nodularin-R and a stable isotope-labeled internal standard.
  
  
  RESULTS
  The validated calibration range was from 0.50 to 100 ng/ml. The intra- and inter-day precision were <6.0 and 9.8%, respectively. The accuracy at the lower limit of quantification (LLOQ) was 2.0%, while for other QC levels, it was <3.4%. The absolute concentrations determined by the LC/MS/MS assay were significantly lower than those measured using a commercial immunoassay. Finally, a variety of demographic factors were evaluated and the findings indicated that the elderly (>50 y) and people living close to seashore or lakefront areas (≤10 km) were the most susceptible to nodularin-R (p=0.79×10(-4) and 2.57×10(-6), respectively).
  
  
  CONCLUSIONS
  This report was among the first to demonstrate that clinical monitoring of nodularin-R could be achieved using LC/MS/MS.
authors.affiliation: Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.forename: Jinhui
authors.initials: J
authors.lastname: Xu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Shanlei
authors.initials: S
authors.lastname: Qiao
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002853:Chromatography, Liquid / Q000379:methods / Q000592:standards*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods / Q000592:standards*; D055815:Young Adult
chemical_list: D010456:Peptides, Cyclic; C063998:nodularin