Determination of Asymmetric Dimethylarginine: Liquid Chromatography–Mass Spectrometry or ELISA?

Nitric oxide (NO) is synthesized in endothelial cells by the enzyme endothelial nitric oxide synthase. The production rate of NO is a key factor for endothelial and cardiovascular functions (1). The substrate of endothelial nitric oxide synthase is Arg, which is converted into the products NO and citrulline. The enzyme is inhibited by the endogenous Arg metabolite asymmetric dimethylarginine (ADMA)(2). Consequently, an increased concentration of ADMA, particularly with an increased ADMA/Arg ratio, leads to a deficiency in endothelial NO production and a subsequent loss of endothelial function(3). This situation occurs in many diseases, such as renal insufficiency, diabetes mellitus, essential hypertension, and hypercholesterolemia(4)(5)(6)(7); therefore, Arg and ADMA are important cardiovascular risk determinants. To independently evaluate the performance of a recently marketed ELISA for the measurement of ADMA (DLD Diagnostika), we compared the ADMA concentrations obtained with this assay with the results from an isotope-dilution liquid chromatography–mass spectrometry (LC-MS) assay(8). After obtaining informed consent, we collected 108 EDTA-plasma samples from 62 individuals. The samples were sorted into 4 groups according to the medical condition of the donors: healthy, end-stage renal failure, hypercholesterolemia, and hypertriglyceridemia (Table 1⇓ ). ADMA concentrations were …