title: Analysis of plasma 3-methoxytyramine, normetanephrine and metanephrine by ultraperformance liquid chromatography-tandem mass spectrometry: utility for diagnosis of dopamine-producing metastatic phaeochromocytoma.
abstract: BACKGROUND
  Measurements of plasma normetanephrine (NMN) and metanephrine (MN) provide a sensitive test for diagnosis of phaeochromocytomas and paragangliomas (PPGLs), but do not allow detection of dopamine-producing tumours. Here we introduce a novel mass spectrometric based method coupled to ultraperformance liquid chromatography (LC-MS/MS) for measuring NMN, MN and 3-methoxytyramine (MTY), the O-methylated metabolite of dopamine.
  
  
  METHODS
  Specific collision-induced fragment ions assessed by multireaction monitoring transitions were used for identification, with quantification according to signal intensities of analytes relative to stable isotope labelled internal standards. Results for solid-phase extracted samples from 196 subjects analysed by LC-MS/MS were compared with those analysed by liquid chromatography with electrochemical detection (LC-ECD). Concentration ranges in 125 volunteers were compared with those from 63 patients with PPGLs, including 14 with metastatic disease.
  
  
  RESULTS
  The LC-MS/MS method showed linearity over four orders of magnitude with analytical sensitivity sufficient to measure to 0.02 nmol/L. Intra- and inter-assay coefficients of variation ranged from 2.8% to 13.5%. NMN and MN were respectively measured 17% and 10% higher and MTY 26% lower by LC-MS/MS than by LC-ECD. Medians and ranges for 3-methoxytramine, NMN and MN were respectively 0.08 (0.03-0.13), 0.35 (0.13-0.95) and 0.15 (0.07-0.33) nmol/L in volunteers. Among patients with PPGLs, plasma methoxytyramine was six-fold higher in patients with than without metastastases (1.09 versus 0.19 nmol/L) and in three patients was the only metabolite increased.
  
  
  CONCLUSIONS
  The LC-MS/MS method enables accurate, selective and sensitive measurements of catecholamine O-methylated metabolites that should be particularly useful for screening and management of dopamine-producing metastatic PPGLs.
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University of Dresden, Fetscherstraße 74, Dresden 01307, Germany. Mirko.Peitzsch@uniklinikum-dresden.de
authors.forename: Mirko
authors.initials: M
authors.lastname: Peitzsch
authors.forename: Aleksander
authors.initials: A
authors.lastname: Prejbisz
authors.forename: Matthias
authors.initials: M
authors.lastname: Kroiß
authors.forename: Felix
authors.initials: F
authors.lastname: Beuschlein
authors.forename: Wiebke
authors.initials: W
authors.lastname: Arlt
authors.forename: Andrzej
authors.initials: A
authors.lastname: Januszewicz
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siegert
authors.forename: Graeme
authors.initials: G
authors.lastname: Eisenhofer
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000097:blood / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D001774:Blood Chemical Analysis / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008676:Metanephrine / Q000097:blood*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009647:Normetanephrine / Q000097:blood*; D010235:Paraganglioma / Q000097:blood / Q000175:diagnosis; D010673:Pheochromocytoma / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D009647:Normetanephrine; D008676:Metanephrine; C001746:3-methoxytyramine; D004298:Dopamine