Liquid chromatographic-mass spectrometric method for simultaneous determination of small organic acids potentially contributing to acidosis in severe malaria
Acidosis is an important cause of mortality in severe falciparum malaria. Lactic acid is a major contributor to metabolic acidosis, but accounts for only one-quarter of the strong anion gap. Other unidentified organic acids have an independent strong prognostic significance for a fatal outcome. In t...
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th-mahidol.311402018-10-19T11:46:43Z Liquid chromatographic-mass spectrometric method for simultaneous determination of small organic acids potentially contributing to acidosis in severe malaria Natthida Sriboonvorakul Natchanun Leepipatpiboon Arjen M. Dondorp Thomas Pouplin Nicholas J. White Joel Tarning Niklas Lindegardh Chulalongkorn University Mahidol University Nuffield Department of Clinical Medicine UCL Biochemistry, Genetics and Molecular Biology Chemistry Acidosis is an important cause of mortality in severe falciparum malaria. Lactic acid is a major contributor to metabolic acidosis, but accounts for only one-quarter of the strong anion gap. Other unidentified organic acids have an independent strong prognostic significance for a fatal outcome. In this study, a simultaneous bio-analytical method for qualitative and quantitative assessment in plasma and urine of eight small organic acids potentially contributing to acidosis in severe malaria was developed and validated. High-throughput strong anion exchange solid-phase extraction in a 96-well plate format was used for sample preparation. Hydrophilic interaction liquid chromatography (HILIC) coupled to negative mass spectroscopy was utilized for separation and detection. Eight possible small organic acids; l-lactic acid (LA), α-hydroxybutyric acid (aHBA), β-hydroxybutyric acid (bHBA), p-hydroxyphenyllactic acid (pHPLA), malonic acid (MA), methylmalonic acid (MMA), ethylmalonic acid (EMA) and α-ketoglutaric acid (aKGA) were analyzed simultaneously using a ZIC-HILIC column with an isocratic elution containing acetonitrile and ammonium acetate buffer. This method was validated according to U.S. Food and Drug Administration guidelines with additional validation procedures for endogenous substances. Accuracy for all eight acids ranged from 93.1% to 104.0%, and the within-day and between-day precisions (i.e. relative standard deviations) were lower than 5.5% at all tested concentrations. The calibration ranges were: 2.5-2500. μg/mL for LA, 0.125-125. μg/mL for aHBA, 7.5-375. μg/mL for bHBA, 0.1-100. μg/mL for pHPLA, 1-1000. μg/mL for MA, 0.25-250. μg/mL for MMA, 0.25-100. μg/mL for EMA, and 30-1500. μg/mL for aKGA. Clinical applicability was demonstrated by analyzing plasma and urine samples from five patients with severe falciparum malaria; five acids had increased concentrations in plasma (range LA=177-1169. μg/mL, aHBA=4.70-38.4. μg/mL, bHBA=7.70-38.0. μg/mL, pHPLA=0.900-4.30. μg/mL and aKGA=30.2-32.0) and seven in urine samples (range LA=11.2-513. μg/mL, aHBA=1.50-69.5. μg/mL, bHBA=8.10-111. μg/mL, pHPLA=4.30-27.7. μg/mL, MMA=0.300-13.3. μg/mL, EMA=0.300-48.1. μg/mL and aKGA=30.4-107. μg/mL). In conclusion, a novel bioanalytical method was developed and validated which allows for simultaneous quantification of eight small organic acids in plasma and urine. This new method may be a useful tool for the assessment of acidosis in patients with severe malaria, and other conditions complicated by acidosis. © 2013 The Authors. 2018-10-19T04:33:40Z 2018-10-19T04:33:40Z 2013-12-15 Article Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. Vol.941, (2013), 116-122 10.1016/j.jchromb.2013.10.005 1873376X 15700232 2-s2.0-84887194249 https://repository.li.mahidol.ac.th/handle/123456789/31140 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84887194249&origin=inward |
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Biochemistry, Genetics and Molecular Biology Chemistry Natthida Sriboonvorakul Natchanun Leepipatpiboon Arjen M. Dondorp Thomas Pouplin Nicholas J. White Joel Tarning Niklas Lindegardh Liquid chromatographic-mass spectrometric method for simultaneous determination of small organic acids potentially contributing to acidosis in severe malaria |
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Acidosis is an important cause of mortality in severe falciparum malaria. Lactic acid is a major contributor to metabolic acidosis, but accounts for only one-quarter of the strong anion gap. Other unidentified organic acids have an independent strong prognostic significance for a fatal outcome. In this study, a simultaneous bio-analytical method for qualitative and quantitative assessment in plasma and urine of eight small organic acids potentially contributing to acidosis in severe malaria was developed and validated. High-throughput strong anion exchange solid-phase extraction in a 96-well plate format was used for sample preparation. Hydrophilic interaction liquid chromatography (HILIC) coupled to negative mass spectroscopy was utilized for separation and detection. Eight possible small organic acids; l-lactic acid (LA), α-hydroxybutyric acid (aHBA), β-hydroxybutyric acid (bHBA), p-hydroxyphenyllactic acid (pHPLA), malonic acid (MA), methylmalonic acid (MMA), ethylmalonic acid (EMA) and α-ketoglutaric acid (aKGA) were analyzed simultaneously using a ZIC-HILIC column with an isocratic elution containing acetonitrile and ammonium acetate buffer. This method was validated according to U.S. Food and Drug Administration guidelines with additional validation procedures for endogenous substances. Accuracy for all eight acids ranged from 93.1% to 104.0%, and the within-day and between-day precisions (i.e. relative standard deviations) were lower than 5.5% at all tested concentrations. The calibration ranges were: 2.5-2500. μg/mL for LA, 0.125-125. μg/mL for aHBA, 7.5-375. μg/mL for bHBA, 0.1-100. μg/mL for pHPLA, 1-1000. μg/mL for MA, 0.25-250. μg/mL for MMA, 0.25-100. μg/mL for EMA, and 30-1500. μg/mL for aKGA. Clinical applicability was demonstrated by analyzing plasma and urine samples from five patients with severe falciparum malaria; five acids had increased concentrations in plasma (range LA=177-1169. μg/mL, aHBA=4.70-38.4. μg/mL, bHBA=7.70-38.0. μg/mL, pHPLA=0.900-4.30. μg/mL and aKGA=30.2-32.0) and seven in urine samples (range LA=11.2-513. μg/mL, aHBA=1.50-69.5. μg/mL, bHBA=8.10-111. μg/mL, pHPLA=4.30-27.7. μg/mL, MMA=0.300-13.3. μg/mL, EMA=0.300-48.1. μg/mL and aKGA=30.4-107. μg/mL). In conclusion, a novel bioanalytical method was developed and validated which allows for simultaneous quantification of eight small organic acids in plasma and urine. This new method may be a useful tool for the assessment of acidosis in patients with severe malaria, and other conditions complicated by acidosis. © 2013 The Authors. |
author2 |
Chulalongkorn University |
author_facet |
Chulalongkorn University Natthida Sriboonvorakul Natchanun Leepipatpiboon Arjen M. Dondorp Thomas Pouplin Nicholas J. White Joel Tarning Niklas Lindegardh |
format |
Article |
author |
Natthida Sriboonvorakul Natchanun Leepipatpiboon Arjen M. Dondorp Thomas Pouplin Nicholas J. White Joel Tarning Niklas Lindegardh |
author_sort |
Natthida Sriboonvorakul |
title |
Liquid chromatographic-mass spectrometric method for simultaneous determination of small organic acids potentially contributing to acidosis in severe malaria |
title_short |
Liquid chromatographic-mass spectrometric method for simultaneous determination of small organic acids potentially contributing to acidosis in severe malaria |
title_full |
Liquid chromatographic-mass spectrometric method for simultaneous determination of small organic acids potentially contributing to acidosis in severe malaria |
title_fullStr |
Liquid chromatographic-mass spectrometric method for simultaneous determination of small organic acids potentially contributing to acidosis in severe malaria |
title_full_unstemmed |
Liquid chromatographic-mass spectrometric method for simultaneous determination of small organic acids potentially contributing to acidosis in severe malaria |
title_sort |
liquid chromatographic-mass spectrometric method for simultaneous determination of small organic acids potentially contributing to acidosis in severe malaria |
publishDate |
2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/31140 |
_version_ |
1763495633477435392 |