Quantification of arginine and its mono- and dimethylated analogs NMMA,ADMA and SDMA in biological fluids by LC–MS/MS: Is LC superfluous?

摘要

Recently,Weaving et al. [9] reported the synthesis of d2-SDMA,d2-ADMA and d2-NMMA and their use as internal standards (IS) for the simultaneous quantification of the endogenous counterparts in human plasma and urine by MS/MS without preceding HPLC separation, i.e., by directly injecting the eluate of SPE extracts into the mass spectrometer. l-Arginine was quantified by the same method using a commercially available d7-l-arginine as the IS [9]. The authors concluded that their method “requires neither sample derivatization nor the need for chromatographic separation of analytes, shows good precision and accuracy and is suited for both research purposes and implementation in the busy, routine clinical laboratory” [9]. In our opinion, this study [9] suffers from many analytical and non-analytical shortcomings. In the present article, we discuss the article byWeaving et al. [9] from the analytical point of view, especially focusing on the importance of the HPLC step in quantitative analysis of l-arginine and its methylated derivates in biological samples and on issues closely related to the LC–MS/MS technique including matrix effects.