Fast and efficient determination of arginine, symmetric dimethylarginine, and asymmetric dimethylarginine in biological fluids by hydrophilic-interaction liquid chromatography-electrospray tandem mass spectrometry

Background:Nitric oxide is synthesized from the amino acid Arg by the enzyme endothelial nitric oxide syn-thase, which is competitively inhibited by the arginine metabolite asymmetric dimethylarginine (ADMA). In this way, increased concentrations of ADMA lead to reduced nitric oxide production associated with a range of cardiac diseases. Research in this field requires the measurement of Arg and of ADMA and its closely related substance, symmetric dimethylarginine (SDMA). Methods: We quantified Arg, ADMA, and SDMA in human plasma, human urine, and cell culture superna-tant by HPLC–electrospray tandem mass spectrometry. Sample preparation required only protein precipitation. Separation was by liquid chromatography on a 150 3 mm silica column with an isocratic mobile phase con