Quantification of hypoglycin A in serum using aTRAQ® assay

Boemer, François; Deberg, Michelle; Schoos, Roland; Baise, Etienne; Amory, Hélène; Gault, G.; Carlier, Jérémy; Gaillard, Yvan; Marcillaud-Pitel, Christel; Votion, Dominique

doi:10.1016/j.jchromb.2015.06.004

Cited by 19 publications

(28 citation statements)

References 12 publications

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“…Using an RP‐C18 column as described in the literature, no baseline separation of HGA and MCPA‐carnitine could be achieved and retention was poor. Other working groups derivatized the amino acid like structure of HGA to improve its retention behaviour . To avoid those (laborious and time‐consuming) derivatization steps, other stationary phases were tested for separation of the underivatized analytes.…”

Section: Resultsmentioning

confidence: 99%

“…Concentrations of the respective calibrators and QCs were chosen with respect to concentrations in serum samples as published by Boemer et al, Bochnia et al, and Sander et al In these references, HGA serum concentrations in AM affected horses ranged from 87 ng/mL to 8493 ng/mL and MCPA‐carnitine concentrations from 42 ng/mL to 166 ng/mL. Additionally, concentrations of the in‐house tested serum samples were taken into consideration for the calibration range, with a mean concentration of 1197 ng/mL (570–2000 ng/mL) for HGA and 63.8 ng/mL (~8.5–150 ng/mL) for MCPA‐carnitine.…”

Section: Resultsmentioning

confidence: 99%

“…Different quantification methods for these analytes were described in the literature . Because of the amino acid like structure of HGA and its metabolite MCPA‐carnitine, the assays were always connected with time‐consuming sample preparation or derivatization steps.…”

Section: Introductionmentioning

confidence: 99%

“…Quantification of HGA, MCPA‐carnitine, and/or other carnitines were described by Sander et al, Valberg et al, and Votion et al after butyl ester formation as part of sample preparation. Boemer et al used the aTRAQ ® assay for quantification of HGA and Bochnia et al derivatized HGA with fluorenylmethoxycarbonyl (fmoc). All working groups employed liquid chromatography (RP C18‐columns) coupled with tandem mass spectrometry (LC–MS/MS) for analysis of prepared samples.…”

Section: Introductionmentioning

confidence: 99%

“…3,7 Different quantification methods for these analytes were described in the literature. 5,[8][9][10][11][12] Because of the amino acid like structure of HGA and its metabolite MCPA-carnitine, the assays were always connected with time-consuming sample preparation or derivatization steps. Carlier et al 9 prepared human whole blood samples with HILIC solid-phase extraction (SPE) followed by dansyl-derivatization.…”

Section: Introductionmentioning

confidence: 99%

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Development and validation of an ultrahigh performance liquid chromatography‐high resolution tandem mass spectrometry quantification method for hypoglycin A and methylene cyclopropyl acetic acid carnitine in horse serum in cases of atypical myopathy

Rudolph

Remane

Wissenbach

et al. 2017

Drug Testing and Analysis

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Atypical myopathy (AM) is a fatal disease in horses presumably caused by hypoglycine A (HGA) from ingested maple seeds and its active metabolite methylene cyclopropyl acetic acid (MCPA). The aim of this study was the development and validation of a rapid and simple assay for HGA and MCPA-carnitine in horse serum and its application to authentic samples. Identification and quantification were carried out by ultra high performance liquid chromatography-high resolution tandem mass spectrometry (UHPLC-HRMS/MS) with full-scan/data-dependent MS/MS. Chromatographic separation was performed by isocratic elution on a hydrophilic interaction liquid chromatography (HILIC) column (100 x 2.1 mm, 1.7 μm). Serum samples (250 μL) were worked up by protein precipitation. The method was validated according to international guidelines with respect to selectivity, linearity, accuracy, precision, matrix effects, and recovery. The calibration range was from 100 to 2000 ng/mL for HGA and from 10 to 1000 ng/mL for MCPA-carnitine. HGA and MCPA-carnitine showed acceptable accuracy and precision (bias -3.0% to 1.1%; RSD 9.2% to 12.4%). The limit of quantification (LOQ) was defined as the lowest calibrator and well below the lowest published serum concentrations in affected horses. Matrix effects ranged from -79% to +20% (RSD 4.2% to 14.4%), recoveries from 17.9% to 21.1% (RSD 2.3% to 10.8 %) for low and high quality control samples, respectively. Applicability was tested in 10 authentic AM cases. In all specimens, relevant amounts of HGA and MCPA-carnitine were found (570-2000 ng/mL; ~8.5-150 ng/mL, respectively). The developed assay allows reliable identification and quantification of HGA and MCPA-carnitine in horse serum and will be helpful to further study the association between HGA/MCPA and AM.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Development and validation of an ultrahigh performance liquid chromatography‐high resolution tandem mass spectrometry quantification method for hypoglycin A and methylene cyclopropyl acetic acid carnitine in horse serum in cases of atypical myopathy

Rudolph

Remane

Wissenbach

et al. 2017

Drug Testing and Analysis

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Quantification of hypoglycin A as butyl ester

Sander

Terhardt

Sander

et al. 2016

Journal of Chromatography B

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Quantification of hypoglycin A and methylenecyclopropylglycine in human plasma by HPLC-MS/MS

Sanford¹,

Isenberg

Carter

et al. 2018

Journal of Chromatography B

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Hypoglycin A (HGA) and methylenecyclopropylglycine (MCPG) are naturally-occurring amino acids known to cause hypoglycemia and encephalopathy. Exposure to one or both toxins through the ingestion of common soapberry (Sapindaceae) fruits are documented in illness outbreaks throughout the world. Jamaican Vomiting Sickness (JVS) and seasonal pasture myopathy (SPM, horses) are linked to HGA exposure from unripe ackee fruit and box elder seeds, respectively. Acute toxic encephalopathy is linked to HGA and MCPG exposures from litchi fruit. HGA and MCPG are found in several fruits within the soapberry family and are known to cause severe hypoglycemia, seizures, and death. HGA has been directly quantified in horse blood in SPM cases and in human gastric juice in JVS cases. This work presents a new diagnostic assay capable of simultaneous quantification of HGA and MCPG in human plasma, and it can be used to detect patients with toxicity from soapberry fruits. The assay presented herein is the first quantitative method for MCPG in blood matrices.

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Quantification of hypoglycin A in serum using aTRAQ® assay

Cited by 19 publications

References 12 publications

Development and validation of an ultrahigh performance liquid chromatography‐high resolution tandem mass spectrometry quantification method for hypoglycin A and methylene cyclopropyl acetic acid carnitine in horse serum in cases of atypical myopathy

Development and validation of an ultrahigh performance liquid chromatography‐high resolution tandem mass spectrometry quantification method for hypoglycin A and methylene cyclopropyl acetic acid carnitine in horse serum in cases of atypical myopathy

Quantification of hypoglycin A as butyl ester

Quantification of hypoglycin A and methylenecyclopropylglycine in human plasma by HPLC-MS/MS

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