Quantitative HPLC-MS/MS analysis of toxins in soapberry (Sapindaceae) seeds: Methylenecyclopropylglycine and Hypoglycin A

Authors: SANFORD, AIMEE - Oak Ridge Institute For Science And Education (ORISE); ISENBERG, SAMANTHA - Centers For Disease Control And Prevention (CDC) - United States; CARTER, MELISSA - Centers For Disease Control And Prevention (CDC) - United States; MOJICA, MIKE - Centers For Disease Control And Prevention (CDC) - United States; MATTHEWS, THOMAS - Centers For Disease Control And Prevention (CDC) - United States; Harden, Leslie - Les; Takeoka, Gary; THOMAS, JERRY - Centers For Disease Control And Prevention (CDC) - United States; PIRKLE, JAMES - Centers For Disease Control And Prevention (CDC) - United States; JOHNSON, RUDOLPH - Centers For Disease Control And Prevention (CDC) - United States

Submitted to: Journal of Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/22/2018
Publication Date: 5/17/2018
Citation: Sanford, A.A., Isenberg, S.L., Carter, M., Mojica, M.A., Matthews, T.P., Harden, L.A., Takeoka, G.R., Thomas, J.D., Pirkle, J.L., Johnson, R.C. 2018. Quantitative HPLC-MS/MS analysis of toxins in soapberry (Sapindaceae) seeds: Methylenecyclopropylglycine and Hypoglycin A. Journal of Food Chemistry. 264:449-454. https://doi.org/10.1016/j.foodchem.2018.04.093.
DOI: https://doi.org/10.1016/j.foodchem.2018.04.093

Interpretive Summary: Consumption of soapberry fruits such as ackee and litchi can induce hypoglycemia, encephalopathy and sometimes death. The causative agents of toxicity in soapberry fruit are the cyclopropyl amino acids, methylenecyclopropylglycine (MCPG) and hypoglycin A (HGA). Seasonal outbreaks of an acute neurologic illness with high mortality among young children occur annually in Muzaffarpur, Bihar, the largest litchi (lychee) fruit cultivation region in India. In collaborative research with the Centers for Disease Control and Prevention (CDC) we recently confirmed that this outbreak of acute hypoglycemic encephalopathy is associated with MCPG/HGA toxicity and litchi consumption. This is the first confirmation that this recurring outbreak of acute hypoglycemic encephalopathy is associated with MCPG/HGA toxicity and litchi consumption. We developed an analytical method capable of quantifying MCPG and HGA levels in soapberry fruits. We previously used this method to quantify MCPG and HGA levels in soapberry arils (the edible portion of the fruit). This work is the first to quantify MCPG and HGA levels in the seeds of soapberry fruits such as rambutan, longan, mamonicillo, ackee and litchi. This knowledge regarding the amounts of MCPG and HGA in fruit is integral for preventing illness outbreaks that are caused by consumption of soapberry fruits.

Technical Abstract: Methylenecyclcopropylglycine (MCPG) and Hypoglycin A (HGA) are naturally occurring amino acids found in various soapberry (Sapindaceae) fruits. These toxins have been linked to illnesses worldwide and were recently implicated in Asian outbreaks of acute hypoglycemic encephalopathy. In a joint agricultural and public health investigation, we developed an analytical method capable of evaluating MCPG and HGA levels in soapberry fruit arils as well as a clinical method for the urinary metabolites of the toxins. Since the initial soapberry method only analyzed the aril portion of the fruit, we present here the extension of the method to include the fruit’s seed matrix. This work is the first method to quantitate both MCPG and HGA levels in the seeds of soapberry fruit, including those collected during a public health investigation. Further, this is the first quantitation of HGA in litchi seeds as well as both toxins in mamoncillo and longan seeds.