title: Performance of plasma free metanephrines measured by liquid chromatography-tandem mass spectrometry in the diagnosis of pheochromocytoma.
abstract: BACKGROUND
  Plasma free metanephrines have proved a highly sensitive biochemical test for the diagnosis of pheochromocytoma. We have developed and validated a simple, LC-MS/MS method to determine plasma metanephrines and compared the diagnostic efficacy of the method with an enzyme immunoassay procedure in 151 patients, 38 with histologically confirmed pheochromocytoma.
  
  
  METHODS
  Off-line solid phase extraction in a 96-well plate format was used to isolate metanephrines from 100-microL of plasma, followed by rapid separation with hydrophilic interaction chromatography. Mass spectrometry detection was performed in multiple-reaction monitoring mode using a tandem quadrupole mass spectrometer with positive electrospray ionization.
  
  
  RESULTS
  Detection limits were <0.1nmol/l with method linearity up to 23.0nmol/L for normetanephrine (NMN), metanephrine (MN) and 3-methoxytyramine (3-MT). Method comparison with an automated LC-MS/MS yielded Deming regression slopes of r=0.94 for NMN, r=0.98 for MN and r=0.94 for 3-MT. Method comparison with enzyme immunoassay revealed regression slope of r=1.28 (NMN) and 1.25 (MN) with values approximately 25% lower than LC-MS/MS. Plasma metanephrines by LC-MS/MS identified all 38 patients with phaeochromocytoma compared with 36 cases by immunoassay.
  
  
  CONCLUSIONS
  Plasma metanephrines measured by LC-MS/MS are a reliable and sensitive test for the biochemical detection of pheochromocytoma.
authors.affiliation: Department of Clinical Biochemistry, Freeman Hospital, Newcastle Hospitals NHS Trust, UK. bob.peaston@nuth.nhs.uk
authors.forename: Robert T
authors.initials: RT
authors.lastname: Peaston
authors.forename: Kendon S
authors.initials: KS
authors.lastname: Graham
authors.forename: Erin
authors.initials: E
authors.lastname: Chambers
authors.forename: Jan C
authors.initials: JC
authors.lastname: van der Molen
authors.forename: Stephen
authors.initials: S
authors.lastname: Ball
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008297:Male; D008676:Metanephrine / Q000097:blood*; D008875:Middle Aged; D010673:Pheochromocytoma / Q000097:blood / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D055815:Young Adult
chemical_list: D008676:Metanephrine