Determination of asymmetric dimethylarginine in biological fluids: a paradigm for a successful analytical story.
OBJECTIVE
To review recently reported analytical methods for the quantification in biological fluids of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthesis, and to evaluate their impact on clinical research.


RESULTS
Recently developed and increasingly used analytical methods in this area are based on mass spectrometry coupled with gas chromatography (i.e., gas chromatography-mass spectrometry and gas chromatography-mass spectrometry/mass spectrometry) or liquid chromatography (i.e., liquid chromatography-mass spectrometry and liquid chromatography-mass spectrometry/mass spectrometry). These approaches revealed asymmetric dimethylarginine concentrations in plasma and serum of healthy adults in the range 400-500 nmol/l. High-performance liquid chromatography methods with fluorescence detection provide asymmetric dimethylarginine plasma/serum concentrations comparable to those of mass spectrometry-based methods. This interval for circulating asymmetric dimethylarginine and the mass spectrometry/mass spectrometry-based methods have the potential to serve as reference values and analytical methods, respectively. An enzyme-linked immunosorbent assay method for asymmetric dimethylarginine has become commercially available and is increasingly used in clinical studies. Comparative studies revealed that the enzyme-linked immunosorbent assay method produces considerably higher asymmetric dimethylarginine concentrations in plasma or serum in healthy humans in the basal state than mass spectrometry and high-performance liquid chromatography methods and runs varyingly in different laboratories.


CONCLUSIONS
At present, many analytical methods allow for the accurate and precise quantification of asymmetric dimethylarginine in biological fluids. However, reliable quantification of biological asymmetric dimethylarginine remains an analytical challenge in basic and clinical research.
Tsikas
Dimitrios
D
Institute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. tsikas.dimitros@mh-hannover.de
D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D004797:Enzyme-Linked Immunosorbent Assay / Q000592:standards; D006801:Humans; D013058:Mass Spectrometry / Q000592:standards; D012016:Reference Values; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction
C018524:N,N-dimethylarginine; D001120:Arginine