title: Determination of asymmetric dimethyl arginine in human serum by liquid chromatography-tandem mass spectrometry: clinical application in hypertensive subjects.
abstract: BACKGROUND
  Asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase plays an important role in endothelial dysfunction processes. Recent studies have linked high ADMA levels with several pathological conditions. The interest as a marker of endothelial dysfunction has increased in the last few years. In this paper, a method for serum ADMA quantification by liquid chromatography tandem mass spectrometry has been described. To test the utility in a pathological condition ADMA levels in hypertensive subjects have been measured.
  
  
  METHODS
  HPLC separation was performed by hydrophilic interaction chromatography using acetonitrile/water containing 0.1% formic acid and 20 mmol/L ammonium formate. Selected reaction monitoring was performed following the transitions m/z 203.1→46.4 for ADMA and 210.1→46.3 for the internal standard [2H7]ADMA.
  
  
  RESULTS
  The method was linear up to 10 μmol/L, limit of detection and limit of quantification were 0.005 μmol/L and 0.01 μmol/L, respectively. Recovery was higher than 96%. Intra- and inter-assay imprecision were lower than 6%. The accuracy, expressed as bias %, was <2.5. ADMA in "healthy" subjects ranged from 0.343 to 0.608 μmol/L and resulted significantly lower than that measured in hypertensive subjects (p<0.001).
  
  
  CONCLUSIONS
  The method developed is selective and sensitive, thus suitable not only for research purposes, but also for routinely work.
authors: Istituto di Biochimica e Biochimica Clinica, Universita` Cattolica del Sacro Cuore, Rome, Italy. jacopo.gervasoni@rm.unicatt.it
authors: Jacopo
authors: J
authors: Gervasoni
authors: Fabio
authors: F
authors: Bonelli
authors: Cecilia
authors: C
authors: Zuppi
authors: Bruno
authors: B
authors: Zappacosta
authors: Alvaro
authors: A
authors: Mordente
authors: Riccardo
authors: R
authors: Calvani
authors: Silvia
authors: S
authors: Persichilli
mesh_terms: D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D006973:Hypertension / Q000097:blood / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: C018524:N,N-dimethylarginine; D001120:Arginine