title: Determination of asymmetric Nα-acetyldimethylarginine in humans: a phase II metabolite of asymmetric dimethylarginine.
abstract: Asymmetric dimethylarginine (ADMA) is produced by protein methylation, a common mechanism of posttranslational protein modification. Elevated levels of ADMA lead to impaired endothelial nitric oxide production and subsequently to a range of cardiovascular and other diseases related to decreased nitric oxide production. Knowledge of the elimination pathways of ADMA and the possibility of influencing them is therefore of major clinical interest. One of these pathways is the N-acetylation and subsequent renal elimination of ADMA in the form of asymmetric Nα-acetyldimethylarginine (Ac-ADMA). In this work, we describe the first method to quantitatively determine Ac-ADMA in human plasma and urine. Ac-ADMA was separated by HPLC on a porous graphitic carbon column and selectively analyzed by tandem mass spectrometry. Ac-ADMA and the internal standard D7-Ac-ADMA were synthesized in-house. Precision and accuracy of the method were better than 5% in plasma and urine quality control samples. First results obtained with this method in samples of healthy volunteers showed plasma levels of 0.643±0.454 nmol/L and urine levels of 152.7±76.7 nmol/L or 13.0±8.9 nmol/mmol creatinine. The method is a suitable tool for investigating this currently mostly neglected ADMA elimination pathway.
authors.affiliation: Institute of Clinical Pharmacology, Otto-von-Guericke University, 39120 Magdeburg, Germany. Electronic address: jens.martens-lobenhoffer@med.ovgu.de.
authors.forename: Jens
authors.initials: J
authors.lastname: Martens-Lobenhoffer
authors.affiliation: University Center for Vascular Medicine, University Hospital Carl Gustav Carus, Technical University, Dresden, Germany.
authors.forename: Roman N
authors.initials: RN
authors.lastname: Rodionov
authors.affiliation: Institute of Clinical Pharmacology, Otto-von-Guericke University, 39120 Magdeburg, Germany.
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Bode-Böger
mesh_terms: D000107:Acetylation; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D001774:Blood Chemical Analysis / Q000379:methods* / Q000592:standards; D002138:Calibration; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012015:Reference Standards; D015203:Reproducibility of Results; D016482:Urinalysis / Q000379:methods* / Q000592:standards; D055815:Young Adult
chemical_list: C018524:N,N-dimethylarginine; D001120:Arginine
keywords: Asymmetric N(α)-acetyldimethylarginine; Asymmetric dimethylarginine; LC–MS/MS; Plasma; Urine