Development and validation of a fast quantitative method for plasma dimethylarginines analysis using liquid chromatography–tandem mass spectrometry

D’Apolito, Oceania; Paglia, Giuseppe; Tricarico, Filomena; Garofalo, Daniela; Pilotti, Alessandra; Lamacchia, Olga; Cignarelli, Mauro; Corso, Gaetano

doi:10.1016/j.clinbiochem.2008.08.075

Cited by 35 publications

(22 citation statements)

References 18 publications

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“…The method employs a small sample volume (25 µl), use of a stable isotope-labeled L-arginine internal standard, a simple sample preparation method with isopropanol (17), and a chromatographic run time of 9 min without the need for derivatization. Our technique complements existing published methods that use HILIC chromatography and LC-MS/MS (13, 18, 19), and builds upon them by: 1) multiplexing the analysis with six analytes and 2) extending our findings to a human population stratified by hsCRP and a mouse model of inflammation.…”

Section: Discussionmentioning

confidence: 95%

Simultaneous Determination of 6 l-Arginine Metabolites in Human and Mouse Plasma by Using Hydrophilic-Interaction Chromatography and Electrospray Tandem Mass Spectrometry

Brown

Becker²,

Wise³

et al. 2011

Clinical Chemistry

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Background Macrophages and related cells are important cellular mediators of the innate system and play an important role in wound healing and fibrosis. Flux through different L-arginine metabolic pathways partially defines the functional behavior of macrophages. Methods to measure metabolites within the nitric oxide synthase/arginase pathways could potentially reveal insights into local and systemic inflammatory processes. Methods A targeted metabolomics approach was developed using HILIC chromatography and electrospray ionization-tandem mass spectrometry to simultaneously measure L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), L-citrulline, L-ornithine, and L-proline in plasma from humans and mice. Results All analytes were quantifiable in human plasma and mouse plasma and serum with a small volume (25µl), minimal sample preparation, and no derivatization. Patients with high plasma concentrations of C-reactive protein and mice with acute inflammation induced by lipopolysaccharide had significant reductions of arginine metabolites in plasma compared with normal controls. Conclusions This new assay uses plasma metabolomic measurements to help provide new insights into metabolic changes coupled to the innate immune response. We identified significant changes in arginine metabolism in both humans and mice following an inflammatory stimulus. These changes were associated with decreased plasma arginine metabolite concentrations and increased methylated arginine concentrations.

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Section: Discussionmentioning

confidence: 95%

Simultaneous Determination of 6 l-Arginine Metabolites in Human and Mouse Plasma by Using Hydrophilic-Interaction Chromatography and Electrospray Tandem Mass Spectrometry

Brown

Becker²,

Wise³

et al. 2011

Clinical Chemistry

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“…The buffering of the samples prior to protein precipitation led to slightly higher and more stable peak intensities in the resulting chromatograms, compared to our previous method without buffering [14]. Other protein precipitation agents, such as methanol with 1% ammonium acetate [12] or methanol:acetonitrile (25:75) [15], were described in the literature. However, the results were comparable with those of our current method in terms of peak shape and absence of interfering peaks.…”

Section: Sample Preparationmentioning

confidence: 96%

Quantification of l-arginine, asymmetric dimethylarginine and symmetric dimethylarginine in human plasma: A step improvement in precision by stable isotope dilution mass spectrometry

Martens‐Lobenhoffer

Bode‐Böger

2012

Journal of Chromatography B

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“…An added value with HILIC in the light that biomarkers can be chemically unstable is that a simple protein precipitation procedure followed by direction injection is feasible for sample preparation. There have been many reports in the literature using this approach for quantitation of biomarkers such as dimethylarginine 100–102, ornithione 103, GABA (γ‐aminobutyric acid) 104, acetylcholine 105, methylalonic acid 89, and so on. Orthogonal sample preparation and chromatographic separation such as RP‐SPE‐HILIC and mixed‐mode SPE‐HILIC have also been employed to achieve extensive sample cleanup in quantitation of melamine 106, nucleosides 107, S ‐adenosylmethionine 58, glutathione 108, etc .…”

Section: Novel Application Of Hilic In Quantitative Bioanalysismentioning

confidence: 99%

Recent advances in application of hydrophilic interaction chromatography for quantitative bioanalysis

Jian

Edom

et al. 2010

J of Separation Science

140

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Hydrophilic interaction chromatography (HILIC) provides a complementary separation mode to RPLC and thus has been gaining increased utilization in LC-MS/MS based quantitative bioanalysis. It has proven to be a powerful tool for separation of polar compounds and has afforded increased selectivity, higher sensitivity, and improved efficiency for quantitation of drug and their metabolites in complex biological matrices. Practical knowledge has been gained for some of the challenges with HILIC applications and effective remedies have been adopted to overcome these challenges. Due to its orthogonality to RPLC, HILIC has been coupled with RP sample preparation or separation techniques, either off-line or on-line to achieve better assay selectivity. The low back-pressure with HILIC enables fast separations under higher flow rates. Small particle columns can be operated under HILIC conditions with regular system back-pressure, eliminating the requirement for ultra-high-pressure liquid chromatographic systems. Matrix effects under HILIC have also been systematically investigated. Effective approaches to reduce or eliminate matrix effects have included optimizing sample preparation, modifying chromatographic conditions, and/or using valve-switching techniques. Finally, the utilization of HILIC is not limited to quantitation of polar drugs and their metabolites, but extended to quantitation of relatively non-polar compounds, peptides and biomarkers.

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Development and validation of a fast quantitative method for plasma dimethylarginines analysis using liquid chromatography–tandem mass spectrometry

Cited by 35 publications

References 18 publications

Simultaneous Determination of 6 l-Arginine Metabolites in Human and Mouse Plasma by Using Hydrophilic-Interaction Chromatography and Electrospray Tandem Mass Spectrometry

Simultaneous Determination of 6 l-Arginine Metabolites in Human and Mouse Plasma by Using Hydrophilic-Interaction Chromatography and Electrospray Tandem Mass Spectrometry

Quantification of l-arginine, asymmetric dimethylarginine and symmetric dimethylarginine in human plasma: A step improvement in precision by stable isotope dilution mass spectrometry

Recent advances in application of hydrophilic interaction chromatography for quantitative bioanalysis

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