Advances in Detecting Ciguatoxins in Fish

Abstract

Ciguatera fish poisoning (CFP) is currently the most common marine biotoxin food poisoning worldwide, associated with human consumption of circumtropical fish and marine invertebrates that are contaminated with ciguatoxins. Ciguatoxins are very potent sodium-channel activator neurotoxins, that pose risks to human health at very low concentrations (>0.01 ng per g of fish flesh in the case of the most potent Pacific ciguatoxin). Symptoms of CFP are nonspecific and intoxication in humans is often misdiagnosed. Presently, there is no medically approved treatment of ciguatera. Therefore, to mitigate the risks of CFP, reliable detection of ciguatoxins prior to consumption of fish tissue is acutely needed, which requires application of highly sensitive and quantitative analytical tests. During the last century a number of methods have been developed to identify and quantify the concentration of ciguatoxins, including in vivo animal assays, cell-based assays, receptor binding assays, antibody-based immunoassays, electrochemical methods, and analytical techniques based on coupling of liquid chromatography with mass spectrometry. Development of these methods, their various advantages and limitations, as well as future challenges are discussed in this review.

Stereoselective Synthesis of the I–L Fragment of the Pacific Ciguatoxins

“…Subsequently, more than 30 other ciguatoxins have been isolated from marine dinoflagellates or from fish and marine organisms that accumulate the toxins by predation. The ciguatoxins can be grouped as Pacific, Caribbean or Indian according the ocean or sea where samples containing each toxin were first collected [3][4][5][6]. Pacific ciguatoxins are the most numerous and well-characterised of the ciguatoxins and this group accounts for more than three quarters of the ciguatoxins that are known [4][5][6].…”

“…The ciguatoxins can be grouped as Pacific, Caribbean or Indian according the ocean or sea where samples containing each toxin were first collected [3][4][5][6]. Pacific ciguatoxins are the most numerous and well-characterised of the ciguatoxins and this group accounts for more than three quarters of the ciguatoxins that are known [4][5][6]. Four Caribbean ciguatoxins have been characterized-C-CTX-1 and C-CTX-2 are equilibrating lactols and C-CTX-3 and C-CTX-4 are diastereomers that arise by reduction of C-CTX-1/C-CTX-2 [7,8].…”

“…Four Caribbean ciguatoxins have been characterized-C-CTX-1 and C-CTX-2 are equilibrating lactols and C-CTX-3 and C-CTX-4 are diastereomers that arise by reduction of C-CTX-1/C-CTX-2 [7,8]. A further eight Caribbean ciguatoxins have been detected by mass spectrometry but have yet to be characterised and the structures of the six ciguatoxins-I-CTX-1-6-isolated from samples collected in the Indian Ocean have yet to be elucidated [6,9,10]. The Pacific ciguatoxins can be divided into two distinct structural sub-groups.…”

Ciguatera Mini Review: 21st Century Environmental Challenges and the Interdisciplinary Research Efforts Rising to Meet Them

“…Generally, toxin analysis includes (i) a semi-quantitative screening method capable of measuring composite toxicity in an action-specific or dose-response manner [ 210 , 211 , 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 ] and (ii) confirmation of CTXs identity either by liquid chromatography tandem-mass spectrometry (LC-MS/MS) or LC coupled to High-Resolution MS (LC-HRMS) [ 36 , 85 , 113 , 183 , 186 , 205 , 210 , 220 , 221 , 222 , 223 ]. However, many different methods (including local folk methods [ 61 , 224 ]) were implemented for the detection of CTXs, as recently reviewed by Pasinszki et al [ 225 ]. Beyond the clinical analysis support, the two-tiered methods/protocols (semi-quantification paired with confirmation) are commonly used for the monitoring of CP risk in the frame of surveillance programs for sample analysis of micro-algae, fish, marine invertebrates, solid-phase adsorption toxin tracking filters, or other artificial surfaces/material with the potential to contain Gambierdiscus/Fukuyoa or CTXs, which have been collected in areas of interest.…”

“…Among analytical techniques suitable for tier two ‘confirmation’, LC-MS/MS is the most utilized for the qualitative (and at times quantitative) determination of CTX analogs due to its capacity for high selectivity and sensitivity in detecting analytes at sub-ppb levels in complex matrices [ 204 , 225 ]. The full implementation of LC-MS methods requires sufficient materials (toxins in natural matrices, reference materials, and analytical standards): (i) to optimize analyte ionization and fragmentation settings, to increase sensitivity for reaching the sub-ppb detection levels required, (ii) to chromatographically resolve different structural analogs (of which there are >30), and (iii) to test the applicability of the method on naturally contaminated and/or spiked samples for method validation (a point that also applies to the tier-one screening methods).…”