A validated method for quantifying hypoglycin A in whole blood by UHPLC–HRMS/MS

Carlier, Jérémy; Guitton, Jérôme; Moreau, Cécile; Boyer, Baptiste; Bévalot, Fabien; Fanton, Laurent; Habyarimana, Jean Belt Adélite; Gault, G.; Gaillard, Yvan

doi:10.1016/j.jchromb.2014.11.029

Cited by 28 publications

(35 citation statements)

References 22 publications

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“…The quantification of hypoglycin A in the blood has also been developed in recent years, using ultra-high performance liquid chromatography-high resolution tandem mass spectrometry. This method has a detection limit of 0.35 µg/L as reported by Carlier, et al [15]. Similar symptoms can be seen with Multiple Acyl-CoA Dehydrogenase Deficiency (MADD).…”

Section: Resultssupporting

confidence: 66%

New Development of Hypoglycemia in a Previously Poorly-Controlled Type 2 Diabetic: Ackee Fruit-Induced Hypoglycemia

Latif¹,

Luthra²

2017

Int J Diabetes Clin Res

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Objective: To report a case of hypoglycemia due to Ackee fruit consumption.Methods: This is a case report and brief review of literature. Results:We report a patient with new onset hypoglycemia due to the consumption of the Ackee fruit. Patient is a 95-year-old Jamaican male with history of uncontrolled, insulin requiring Type 2 diabetes mellitus. He presented with new onset of hypoglycemia and improvement in hemoglobin A1C without any changes in diabetes regimen, other medications or co-morbidities. On investigative questioning, he reported that he had recently received a jar of preserved Ackee fruit, and was consuming small portions of it daily. This coincided with the development of hypoglycemia. Conclusion:Despite being uncommonly used in the United States, Ackee fruit consumption is a known cause of hypoglycemia. Ackee fruit contains two toxins, hypoglycin A and hypoglycin B that work through the same mechanism to deplete hepatic glycogen stores and cause refractory hypoglycemia. The most severe form of Ackee-fruit toxicity is known as "Jamaican Vomiting Sickness". The disorder is characterized by symptoms of severe hypoglycemia and seizures, ultimately leading to coma and death. Although rare in the United States, it is important to understand and recognize the symptoms of Ackee fruit induced toxicity to avoid late detection and severe complications.

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Section: Resultssupporting

confidence: 66%

New Development of Hypoglycemia in a Previously Poorly-Controlled Type 2 Diabetic: Ackee Fruit-Induced Hypoglycemia

Latif¹,

Luthra²

2017

Int J Diabetes Clin Res

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“…15,34 In horses however, dansyl derivatives of hypoglycin A were identified in blood using UHPLC-MS/MS. 35 Additionally, TMS derivatives of MCPA-carnitine in serum and MCPA-Gly were detected in the urine of horses exhibiting seasonal pasture myopathy caused by hypoglycin A ingestion. 36 …”

Section: Introductionmentioning

confidence: 98%

Quantification of Metabolites for Assessing Human Exposure to Soapberry Toxins Hypoglycin A and Methylenecyclopropylglycine

Isenberg

Carter

Graham

et al. 2015

Chem. Res. Toxicol.

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Ingestion of soapberry fruit toxins hypoglycin A and methylenecyclopropylglycine has been linked to public health challenges worldwide. In 1976, over 100 years after Jamaican Vomiting Sickness (JVS) was first reported, the cause of JVS was linked to the ingestion of the toxin hypoglycin A produced by ackee fruit. A structural analog of hypoglycin A, methylenecyclopropylglycine (MCPG), was implicated as the cause of an Acute Encephalitis Syndrome (AES). Much of the evidence linking hypoglycin A and MCPG to these diseases has been largely circumstantial due to the lack of an analytical method for specific metabolites. This study presents an analytical approach to identify and quantify specific urine metabolites for exposure to hypoglycin A and MCPG. The metabolites are excreted in urine as glycine adducts methylenecyclopropylacetyl-glycine (MCPA-Gly) and methylenecyclopropylformyl-glycine (MCPF-Gly). These metabolites were processed by isotope-dilution, separated by reverse-phase liquid chromatography, and monitored by electrospray-ionization tandem mass spectrometry. The analytical response ratio was linearly proportional to the concentration of MCPF-Gly and MCPA-Gly in urine from 0.10 to 20 μg/mL with a correlation coefficient of r > 0.99. The assay demonstrated accuracy ≥ 80 % and precision ≤ 20 % RSD across the calibration range. This method has been applied to assess exposure to hypoglycin A and MCPG as part of a larger public health initiative and was used to provide the first reported identification of MCPF-Gly and MCPA-Gly in human urine.

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“…A method comparison with the method described by Carlier et al [12] has also been achieved. Both procedures require meticulous sample preparation and show similar capacities (reproducibility, specificity .…”

Section: Resultsmentioning

confidence: 99%

“…Results generated by the here-above described method were compared with another recently developed sensitive quantification method of hypoglycin A in whole blood using an UHPLC-HRMS/MS technique [12]. Slope and intercept were estimated by Passing & Bablok regression with Medcalc v12.1 software.…”

Section: Methods Comparisonmentioning

confidence: 99%