Development and validation of a UHPLC-MS/MS method for measurement of a gut-derived uremic toxin panel in human serum: An application in patients with kidney disease
| Autor: | Raymond E. West, Alexander J. Prokopienko, Jason R. Stubbs, Thomas D. Nolin |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Quality Control
Time Factors Electrospray ionization Clinical Biochemistry Pharmaceutical Science Sulfuric Acid Esters Mass spectrometry Kynurenic Acid 01 natural sciences Article Analytical Chemistry chemistry.chemical_compound Cresols Kynurenic acid Risk Factors Tandem Mass Spectrometry Drug Discovery Ammonium formate Humans Sulfate Spectroscopy Chromatography High Pressure Liquid Uremia Chromatography 010405 organic chemistry Hippurates 010401 analytical chemistry Selected reaction monitoring Hippuric acid Reproducibility of Results Hydrogen-Ion Concentration 0104 chemical sciences Standard curve chemistry Solvents Kidney Diseases Indican Blood Chemical Analysis |
| Zdroj: | J Pharm Biomed Anal |
| Popis: | Gut-derived uremic toxins contribute to the uremic syndrome and are gaining attention as potentially modifiable cardiovascular disease risk factors in patients with underlying chronic kidney disease. A simple, rapid, robust, accurate and precise ultra-performance liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous determination of a panel of four gut-derived uremic toxins in human serum. The panel was comprised of kynurenic acid, hippuric acid, indoxyl sulfate, and p-cresol sulfate. Serum samples were protein precipitated with acetonitrile containing deuterated internal standards. Chromatographic separation of analytes was accomplished with an Acquity BEH C18 (2.1 × 100 mm, 1.7 μm) column by isocratic elution at a flow rate of 0.3 mL/min with a mobile phase composed of solvent A (10 mM ammonium formate; pH 4.3) and solvent B (acetonitrile) (85:15, v/v). Analytes were detected using heated electrospray ionization and selected reaction monitoring. The total run-time was 4 minutes. Standard curves were linear and correlation coefficients (r) were ≥0.997 for concentration ranges of 0.01–0.5 μg/mL for kynurenic acid, 0.25–80 μg/mL for p-cresol sulfate, and 0.2–80 μg/mL for hippuric acid and indoxyl sulfate. Intra- and inter-day accuracy and precision were within 19.3% for the LLOQs and ≤10.9% for all other quality controls. Matrix effect from serum was |
| Databáze: | OpenAIRE |
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