Measurement of arginine derivatives in pediatric patients with chronic kidney disease using high-performance liquid chromatography-tandem mass spectrometry

Background: The arginine derivatives asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) interfere with endothelial nitric oxide synthesis. Plasma ADMA and SDMA have been shown to be risk factors for cardiovascular disease and/or kidney function deterioration in a variety of patient populations. Methods: We developed a method to quantitatively measure arginine, ADMA, and SDMA using HPLC-tandem mass spectrometry. C-13(6),-L-Arginine was used as the internal standard, while the derivatives were separated on a silica column in less than 14 min. Plasma levels of ADMA, SDMA, and arginine were measured in children with stage II or III chronic kidney disease (CKD) and age- and gender-matched siblings. Results: The chromatography exhibited no observable ion suppression in the patient specimens tested. There was no apparent carryover for any of the analytes. The assay was linear over 0.32-2.29, 0.23-4.43, and 1.00-303.89 mu mol/L for ADMA, SDMA, and arginine, respectively. Plasma ADMA, SDMA, and arginine (mean SD) were 1.10 +/- 0.35, 2.06 +/- 1.11, and 57.93 +/- 22.10 mu mol/L for children with CKD, and 0.78 +/- 0.16, 0.71 +/- 0.23, and 65.29 +/- 21.30 mu mol/L for the healthy siblings. Conclusions: The method exhibited no observable ion suppression in the patient specimens tested and has an acceptably short analytical cycle time. Children with CKD had higher levels of ADMA and SDMA than the healthy siblings.