A new method for quantifying causative and diagnostic markers of methylenecyclopropylglycine poisoning.
Abstract: Up to now quantification of hypoglycin A in serum and urine in the range of nmols to μmols per liter plus the measurement of accumulated acyl conjugates have been used for the diagnosis of poisoning by fruits or seeds of in humans and animals. A second poison, methylenecyclopropylglycine, however, is known to occur in this material. The objective of our study was to develop and evaluate a method for the quantification of this compound suitable for test materials obtained from animals and man. Methods: Methylenecyclopropylglycine was extracted from serum and urine of a volunteer by a methanolic solution containing labeled methylenecyclopropylglycine as internal standard. UPLC-MS/MS analysis was performed after butylation. Results: Lower limits of detection and quantification were found at 0.5 and 2.5 nmol/L respectively in both urine and serum for each of two isomers, linearity of results (r > 0.998) was demonstrated for the range of 0.5-500 nmol/L in urine and serum.The method was applied to urine and serum of horses poisoned by seeds, methylenecyclopropylglycine was found in addition to hypoglycin A. Methylenecyclopropylformyl glycine, a metabolite of methylenecyclopropylglycine, however, was present in much higher concentrations than methylenecyclopropylglycine in all but one samples. Conclusions: Quantification of methylenecyclopropylglycine can be successfully integrated into our established analytical procedure used for clinical diagnosis of poisoning. The extended method will improve disease evaluation in humans and animals.
Publication Date: 2019-08-05 PubMed ID: 31440457PubMed Central: PMC6699453DOI: 10.1016/j.toxrep.2019.08.002Google Scholar: Lookup
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Summary
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The research article discusses a newly developed method to detect and measure the amount of methylenecyclopropylglycine, a poisonous compound found in certain fruits or seeds, in both human and animal samples.
Objective and Methods of the Study
- The primary aim of the study is to formulate and assess a procedure that can be used to quantify methylenecyclopropylglycine in samples acquired from humans and animals. This harmful compound is noted to be present in certain fruits and seeds and is associated with poisoning cases.
- The research team developed a method where methylenecyclopropylglycine was extracted from the urine and serum sample of a volunteer. A methanolic solution containing a labeled version of the same compound served as an internal standard.
- Post extraction, Ultra Performance Liquid Chromatography – Tandem Mass Spectrometry (UPLC-MS/MS) analysis was conducted after the process of butylation.
Results of the Study
- The lower limits for detection and quantification of methylenecyclopropylglycine were found to be 0.5 and 2.5 nmol/L respectively in both urine and serum samples.
- Linearity of results (with a correlation coefficient ‘r’ value greater than 0.998) was demonstrated for a range of 0.5-500 nmol/L in both urine and serum, indicating a strong linear relationship between observed and predicted values.
- On applying this method to serum and urine samples of horses poisoned by seeds, both hypoglycin A and methylenecyclopropylglycine were found, showcasing the applicability of the developed method in real-world scenerios.
- Intriguingly, methylenecyclopropylformyl glycine – a metabolite of methylenecyclopropylglycine, was present in much higher concentrations than methylenecyclopropylglycine in almost all samples.
Conclusions
- The researchers concluded that the quantification of methylenecyclopropylglycine can be successfully integrated into the existing analytical protocol used for the clinical diagnosis of poisoning.
- The newly developed method offers potential for improved disease evaluation in both humans and animals by permitting detection and measurement of additional causative agents of poisoning.
Cite This Article
APA
Sander J, Terhardt M, Sander S, Aboling S, Janzen N.
(2019).
A new method for quantifying causative and diagnostic markers of methylenecyclopropylglycine poisoning.
Toxicol Rep, 6, 803-808.
https://doi.org/10.1016/j.toxrep.2019.08.002 Publication
Researcher Affiliations
- Screening-Labor Hannover, Ronnenberg, Germany.
- Screening-Labor Hannover, Ronnenberg, Germany.
- Screening-Labor Hannover, Ronnenberg, Germany.
- Institute for Animal Nutrition, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
- Screening-Labor Hannover, Ronnenberg, Germany.
- Department of Clinical Chemistry, Hannover Medical School, Hannover, Germany.
Conflict of Interest Statement
None.
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Citations
This article has been cited 3 times.- Sander J, Terhardt M, Janzen N, Renaud B, Kruse CJ, François AC, Wouters CP, Boemer F, Votion DM. Tissue Specific Distribution and Activation of Sapindaceae Toxins in Horses Suffering from Atypical Myopathy.. Animals (Basel) 2023 Jul 26;13(15).
- Sander J, Terhardt M, Janzen N. Severe Inhibition of Long-Chain Acyl-CoA Enoylhydratase (EC 4.2.1.74) in a Newborn Foal Suffering From Atypical Myopathy.. Front Vet Sci 2021;8:765623.
- Bochnia M, Ziemssen E, Sander J, Stief B, Zeyner A. Methylenecyclopropylglycine and hypoglycin A intoxication in three Pére David's Deers (Elaphurus davidianus) with atypical myopathy.. Vet Med Sci 2021 May;7(3):998-1005.
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