Mass spectrometric quantification of L-arginine and its pathway related substances in biofluids: the road to maturity

The amino acid L-arginine together with its metabolites and related substances is in the center of many biologically important pathways, especially the urea cycle and the nitric oxide (NO) synthesis. Therefore, the concentrations of these substances in various biological fluids are of great interest as predictive markers for health and disease. Yet, they provide major analytical difficulties as they are very polar in nature and therefore not easily to be separated on standard reversed phase HPLC stationary phases. Furthermore, as endogenous substances, no analyte-free matrix is available, a fact that results in complicated calibration procedures. This review evaluates the analytical literature for the determination of L-arginine, symmetric dimethylarginine, asymmetric dimethylarginine, monomethylarginine, L-citrulline, L-ornithine, L-homoarginine, agmatine and dimethylguanidinovaleric acid in biological fluids. Papers are discussed, which were published since 2007 and describe methods applying capillary electrophoresis (CE), gas chromatography (GC), reversed phase HPLC or polar phase HPLC, coupled to mass spectrometric quantification. Nowadays, many carefully developed and validated methods for L-arginine and its related substances are available to the scientific community. The use of stable isotope labeled internal standards enables high precision and accuracy in mass spectrometry-based quantitative analysis.