A novel mass spectrometry‐based method for simultaneous determination of asymmetric and symmetric dimethylarginine, <scp>l</scp>‐arginine and <scp>l</scp>‐citrulline optimized for LC‐MS‐TOF and LC‐MS/MS

Wiśniewski, Jerzy; Fleszar, Mariusz G.; Piechowicz, Joanna; Krzystek−Korpacka, Małgorzata; Chachaj, Angelika; Szuba, Andrzej; Lorenc-Kukuła, Katarzyna; Masłowski, Leszek; Witkiewicz, Wojciech; Gamian, Andrzej

doi:10.1002/bmc.3994

Cited by 19 publications

(17 citation statements)

References 38 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By addition of an isotope labelled internal standard for each measured amino acid, the problem of small ionization efficiency fluctuations can be eliminated. Isotope labelled amino acids for hydrolysed samples are commercially available, but their use as internal standards has been limited to a relatively small number of compounds and studies [ 27 , 33 , 34 ]. To the best of our knowledge, stable isotopes of the oxidized sulphur-containing amino acids methionine sulfone and cysteic acid, which are present in oxidized samples, have never before been used as internal standards.…”

Section: Discussionmentioning

confidence: 99%

High-throughput analysis of amino acids in plant materials by single quadrupole mass spectrometry

et al. 2018

View full text Add to dashboard Cite

BackgroundThe amino acid profile of plants is an important parameter in assessments of their growth potential, resource-use efficiency and/or quality as food and feed. Screening studies may involve large number of samples but the classical amino acid analysis is limited by the fact that it is very time consuming with typical chromatographic run times of 70 min or more.ResultsWe have here developed a high-throughput method for analysis of amino acid profiles in plant materials. The method combines classical protein hydrolysis and derivatization with fast separation by UHPLC and detection by a single quadrupole (QDa) mass spectrometer. The chromatographic run time is reduced to 10 min and the precision, accuracy and sensitivity of the method are in line with other recent methods utilizing advanced and more expensive mass spectrometers. The sensitivity of the method is at least a factor 10 better than that of methods relying on detection by fluorescence or UV. It is possible to downscale sample size to 20 mg without compromising reproducibility, which makes the method ideal for analysis of very small sample amounts.ConclusionThe developed method allows high-throughput analysis of amino acid profiles in plant materials. The analysis is robust and accurate as well as compatible with both free amino acids and protein hydrolysates. The QDa detector offers high sensitivity and accuracy, while at the same time being relatively simple to operate and cheap to purchase, thus significantly reducing the overall analytical costs compared to methods based on more advanced mass spectrometers.Electronic supplementary materialThe online version of this article (10.1186/s13007-018-0277-8) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

High-throughput analysis of amino acids in plant materials by single quadrupole mass spectrometry

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Before the administration of the rst dose of the metformin and after: 6, 12, 15 weeks of the treatment, the blood concentration of metformin, as well as the compounds related to the production of nitric oxide were assessed for group A and B. The wide panel of L-arginine/NO pathway metabolites (L-arginine, Lcitrulline, ADMA -asymmetric dimethylarginine, DMA -dimethylamine, SDMA -symmetric dimethylarginine, ornithine) were assessed by a recently developed novel assay (25), using the liquid chromatography-mass spectrometry technique (LC-MS/MS).…”

Section: Methodsmentioning

confidence: 99%

Metformin Has No Impact on Nitric Oxide Production in Patients With Pre-diabetes

Sutkowska

Fortuna

Kałuża

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: The effect of metformin on vascular system is still not fully understood and the studies performed on animals have suggested possible impact on the nitric oxide (NO) bioavailability. Aim: The evaluation of different doses of metformin impact on NO production in people with pre-diabetes.Methods: The metformin-naïve patients from one Diabetic Center with new-diagnosed pre-diabetes, without cardio-vascular diseases, were randomised (regarding to the identification number, individual for each inhabitant in the country) for treatment with different doses of metformin (group A 3 x 500 mg, group B 3 x 1000mg) for 15 weeks. The wide panel of L-arginine/NO pathway metabolites concentrations was assessed using the LC-MS/MS. Results: Between October 2017 and December 2018, 36 individuals were initially randomised to intervention groups, but 25 accomplished the study: 14 patients in group A, 11 in group B; also 11 healthy volunteers were recruited. There was no difference between participants with pre-diabetes and healthy volunteers as regards the baseline characteristics except for fasting glucose and fatty liver. The decrease of L-citrulline concentration only was reported for treatment groups during the intervention period, with no change for the other NO-production related substances.Conclusions: It was the first study on the in vivo release of NO in humans at different metformin doses, in patients with pre-diabetes. Metformin has no impact on NO production irrespective of the dose. The citrulline concentration change can indicate the drug impact on altered enterocytes’ condition. The small number of patients is a limitation of the study.Trial registration: ClinicalTrials; number: NCT03398356; retrospectively registered- date of registration:01 July 2018; https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0007ODV&selectaction=Edit&uid=U0003WJC&ts=4&cx=1y9eeb

show abstract

“…The concentrations of amide derivative ARG, citrulline, ADMA, and SDMA were measured simultaneously by highperformance liquid chromatography (HPLC) with mass spectrometry detection. 16 All the separations were performed with the HPLC system Agilent Technologies 1260 Infinity (Agilent Technologies, Santa Clara, USA). The Acquity UPLC HSS T3 50 × 1.0 mm, 1.8 μm column from Waters (Milliford, USA) was used throughout the chromatographic separation.…”

Section: Blood Enzymes Arginine and Its Derivatives And Citrullinementioning

confidence: 99%

The impact of sitagliptin, inhibitor of dipeptidyl peptidase-4 (DPP-4), on the ADMA-DDAH-NO pathway in ischemic and reperfused rat livers

Trocha¹,

Nowak²,

Merwid-Ląd³

et al. 2018

Adv Clin Exp Med

Self Cite

View full text Add to dashboard Cite

Background. A correlation between the level of asymmetric dimethylarginine (ADMA)-the inhibitor of the nitric oxide (NO) synthesis-and the liver function and survival after a liver transplantation has been reported. Objectives. The aim of this study was to evaluate the effect of sitagliptin-the inhibitor of dipeptidyl peptidase-4 (DPP-4)-on the NO-ADMA-dimethylarginine dimethylaminohydrolase (DDAH) pathway in rat livers subjected to ischemia/reperfusion (IR). Material and methods. The rats received sitagliptin (5 mg/kg, per os-p.o.) (groups: Slivers not subjected to IR procedure, and SIR-livers subjected to IR procedure) or a saline solution (groups: C-livers not subjected to IR procedure, and CIR-livers subjected to IR procedure) for 14 days; following this, livers in the SIR and CIR groups were subjected to ischemia (60 min) and reperfusion (24 h). Aminotransferases were measured before the surgery; additionally, the arginine (ARG), ADMA and symmetric dimethylarginine (SDMA) levels were estimated just before ischemia and during reperfusion (at 0.5 h, 4 h and 24 h). After IR, citrulline, the DDAH activity, mRNA for type 1 DDAH (DDAH1), and arginine methyltransferase type 1 (PRMT1) were determined. Results. The increase in the initial level of ARG/ADMA0 (A/A) ratio in group S compared to group C verged on statistical significance. At 0.5 h and 4 h of reperfusion, the highest concentration of ADMA was found in group CIR. At those time points, the ARG level and the A/A ratio were decreased in groups CIR and SIR as compared to groups C and S, respectively. The alanine transaminase (ALT) activity was lower in the sitagliptintreated group than in the non-treated one. The DDAH and citrulline levels were reduced in group CIR as compared to group C, but were greater in group SIR as compared to group S. The PRMT1 mRNA expression was higher in groups CIR and SIR, compared to groups C and S, respectively. Conclusions. The increased A/A ratio suggests a protective effect of sitagliptin on livers not subjected to IR. Changes in the DDAH activity and the PRMT1 mRNA expression also imply the protective activity of sitagliptin during IR.

show abstract

A novel mass spectrometry‐based method for simultaneous determination of asymmetric and symmetric dimethylarginine, l‐arginine and l‐citrulline optimized for LC‐MS‐TOF and LC‐MS/MS

Cited by 19 publications

References 38 publications

High-throughput analysis of amino acids in plant materials by single quadrupole mass spectrometry

High-throughput analysis of amino acids in plant materials by single quadrupole mass spectrometry

Metformin Has No Impact on Nitric Oxide Production in Patients With Pre-diabetes

The impact of sitagliptin, inhibitor of dipeptidyl peptidase-4 (DPP-4), on the ADMA-DDAH-NO pathway in ischemic and reperfused rat livers

Contact Info

Product

Resources

About