A Generic LC-HRMS Screening Method for Marine and Freshwater Phycotoxins in Fish, Shellfish, Water, and Supplements - PubMed
- ️Fri Jan 01 2021
A Generic LC-HRMS Screening Method for Marine and Freshwater Phycotoxins in Fish, Shellfish, Water, and Supplements
Mirjam D Klijnstra et al. Toxins (Basel). 2021.
Abstract
Phycotoxins occur in various marine and freshwater environments, and can accumulate in edible species such as fish, crabs, and shellfish. Human exposure to these toxins can take place, for instance, through consumption of contaminated species or supplements and through the ingestion of contaminated water. Symptoms of phycotoxin intoxication include paralysis, diarrhea, and amnesia. When the cause of an intoxication cannot directly be found, a screening method is required to identify the causative toxin. In this work, such a screening method was developed and validated for marine and freshwater phycotoxins in different matrices: fish, shellfish, water, and food supplements. Two LC methods were developed: one for hydrophilic and one for lipophilic phycotoxins. Sample extracts were measured in full scan mode with an Orbitrap high resolution mass spectrometer. Additionally, a database was created to process the data. The method was successfully validated for most matrices, and in addition, regulated lipophilic phycotoxins, domoic acid, and some paralytic shellfish poisoning toxins could be quantified in shellfish. The method showed limitations for hydrophilic phycotoxins in sea water and for lipophilic phycotoxins in food supplements. The developed method is a screening method; in order to confirm suspected compounds, comparison with a standard or an additional analysis such as NMR is required.
Keywords: HILIC; food supplements; high resolution mass spectrometry; phycotoxins; reversed phase; screening; shellfish; water.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
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Workflows for the different matrices and toxin groups. All steps were developed and optimized during this research, except for the clean-up of hydrophilic toxins in food supplements (shown in the white text box).
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Average relative recoveries (n = 2, error bars represent the min and max values) of lipophilic phycotoxins with various extraction methods, compared to a triple extraction with methanol and vortex mixing. Extraction A: 4 mL methanol (MeOH), followed by the second step with 4 mL water/acetonitrile/ammonium formate/formic acid (H2O/ACN/Amm.form/FA) (55:45 v/v, 2 mM, 0.5 mM). Extraction B: 4 mL H2O/ACN/Amm.form/FA (55:45 v/v, 2 mM, 0.5 mM), followed by the second step with 4 mL methanol.
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Average relative recoveries (n = 2, error bars represent the min and max values) of toxins with two extraction methods. Recoveries of the tested extractions are compared to those of three different in-house methods (see text).
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Average relative recoveries (n = 2, error bars represent the min and max values) of SPX1 and GYM after algal disruption. Recovery of the SPE treatment is set at 100%.
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Average recoveries (n = 2, error bars represent the min and max values) of lipophilic phycotoxins in water after solid phase extraction.
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Average recoveries (n = 2) of hydrophilic phycotoxins by HILIC solid phase extraction with (A) a sample load with 75% organic strength and (B) a sample load with 90% organic strength. The recovery is absolute and total recovery should be 100%.

Reconstructed chromatograms of the applied reversed phase liquid chromatography of (A) azaspiracids, spirolides, pinnatoxins, gymnodimine, and okadaic acid esters measured in the positive ionization mode; (B) domoic acid, microcystins, ciguatoxins, brevetoxins, pectenotoxin, and palytoxin measured in the positive ionization mode; (C) yessotoxins, okadaic acid, and dinophysistoxins measured in the negative ionization mode. The blue line is % of mobile phase B.

Reconstructed chromatograms of the hydrophilic interaction liquid chromatography of (A) anatoxin (ATX), cylindrospermopsin (CYN), domoic acid (DA), tetrodotoxin (TTX), saxitoxin (STX) decarbamoylsaxitixin (dcSTX), neosaxitoxin (NEO), and decarbamoylsaxitoxin (dcNEO) measured in the positive ionization mode; (B) N-sulfocarbamoylgonyautoxin 2 (C1) and 3 (C2), gonyautoxin 2, 3, and 5 (GTX2, 3, and 5), measured in the negative ionization mode; (C) decarbamoylgonyautoxin 2 and 3 (dcGTX2 and 3) measured in the negative ionization mode; (D) gonyautoxin 1 and 4 (GTX1 and 4) measured in the negative ionization mode. The blue line is % of mobile phase B.
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Schematic overview of the HRMS method.
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