title: Quantification of L-arginine, asymmetric dimethylarginine and symmetric dimethylarginine in human plasma: a step improvement in precision by stable isotope dilution mass spectrometry.
abstract: The amino acid L-arginine and its metabolites ADMA and SDMA are important markers for a range of diseases in humans. Increased levels of ADMA and SDMA in plasma point to endothelial dysfunction, hypertension, renal impairment and other pathological states. We present here a method to quantify L-arginine, ADMA and SDMA in human plasma, which is suitable to support clinical research in this field. Sample preparation consisted only of protein precipitation and the analytes were separated using a silica based HILIC column. The analytes were detected by ESI MS/MS, providing high selectivity and sensitivity. The calibration functions were linear in the ranges of 7.5-150 μmol/l for l-arginine, 0.15-3 μmol/l for ADMA and 0.2-4 μmol/l for SDMA. These ranges cover the concentrations encountered in healthy and pathological human plasma. The method employs (13)C(6)-arginine, D(7)-ADMA and, for the first time in LC-MS/MS, D(6)-SDMA as internal standards for L-arginine, ADMA and SDMA. Therefore, matrix independency and a high intra-day precision of 0.82% for L-arginine, 2.12% for ADMA and 2.83% for SDMA, were achieved at basal plasma concentrations. The respective inter-day precision values were 4.01% for l-arginine, 3.77% for ADMA and 3.86% for SDMA.
authors.affiliation: Institute of Clinical Pharmacology, Otto-von-Guericke University, Magdeburg, Germany. jens.martens-lobenhoffer@med.ovgu.de
authors.forename: Jens
authors.initials: J
authors.lastname: Martens-Lobenhoffer
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Bode-Böger
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D001120:Arginine