Saxitoxin dihydrochloride

371.0875575

VKS19V6FQN

DTXSID60189042

White solid

Very soluble in water|Very soluble in methanol; sparingly soluble in ethanol, glacial acetic acid; practically insoluble in lipid solvents|Very soluble in methanol; slightly soluble in ethanol, glacial acetic acid; insoluble in alkalies

log Kow: -4.22. Miscible with water at 25 °C. VP: 8.03X10-15 mm Hg at 25 °C (est) /Saxitoxin hydrate; 35523-89-8/

pKa in water: 8.24, 11.60|MW: 299. pKa1 8.2; pKa2 11.3 ... polar nature allows it to dissolve readily in water and lower alcohols ... insoluble in organic solvents ... stable in neutral and acidic solutions /Saxitoxin/

Hygroscopic. Stable in acid solutions; decomposes rapidly in alkaline media|log Kow = -2.44. VP: 1.83X10-13 mm Hg at 25 °C. Solubility in water: 7.43X10+4 mg/L at 25 °C (est) /Saitoxin/|Noncrystalline solid. MW: 299.34. MF: C10H17N7O4 /Saxitoxin hydrate; 35523-89-8/

The toxin is an alkaloid and is relatively heat-stable.

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

/Saxitoxin/ ... during red tides blooms may reach 20 million to 40 million per milliliter(1). /Saxitoxin/

IDENTIFICATION AND USE: Saxitoxin dihydrochloride (STX) is a white solid. Saxitoxin and its derivatives, collectively referred to as paralytic shellfish toxins (PSTs), are unique among neurotoxins in that they are found in both marine and freshwater environments. Prokaryotic cyanobacteria are responsible for PST production in freshwater systems, while eukaryotic dinoflagellates are the main producers in marine waters. Bioaccumulation by filter-feeding bivalves and fish and subsequent transfer through the food web results in the potentially fatal human illnesses, paralytic shellfish poisoning and saxitoxin pufferfish poisoning. It is used as a tool in neurochemical research. STX is listed in schedule 1 of the Chemical Weapons Convention. HUMAN STUDIES: Exposure to saxitoxin most commonly occurs following ingestion of certain fish that contain it in their tissues. Ingestion of saxitoxin can cause numbness of the oral mucosa as quickly as 30 minutes after exposure. In severe poisoning, illness typically progresses rapidly and may include gastrointestinal (nausea, vomiting) and neurological (cranial nerve dysfunction, a floating sensation, headache, muscle weakness, paresthesias and vertigo) signs and symptoms. Respiratory failure and death can occur from paralysis. Much is known about the toxin sources, primarily certain dinoflagellate species, and there is extensive information on toxin transfer to traditional vectors - filter-feeding molluscan bivalves. Non-traditional vectors, such as puffer fish and lobster, may also pose a risk. ANIMAL STUDIES: In rats sublethal dose of STX administered intraperitoneally results in an acute alteration of dopamine (DA) production and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). In rats after systemic administration of the STX, it reaches the brain producing alterations in neurotransmission increasing the levels of serotonin. ECOTOXICITY STUDIES: STX produced by toxic dinoflagellates enter the cytoplasm and induce apoptosis of oyster immune cells through a caspase-dependent pathway. STX disturbed the normal growth of medaka embryos probably by affecting the metabolic rate in the exposed medaka embryos. Fish detect extremely low levels of STX via the specialized gustatory receptor(s). Physiological and pharmacological studies show that receptor(s) for STX are distinct from those which detect feeding stimulant amino acids and bile acids.

Saxitoxins (STXs) are potent neurotoxins that block voltage-gated channels in neurons and induce cytotoxicity. These toxins not only can generate reactive oxygen species but also can alter antioxidant levels, promoting oxidative stress. Under this pro-oxidant situation, the use of the antioxidant lipoic acid (LA) can represent a chemoprotective alternative to minimize the deleterious effects induced by neurotoxins as STXs. P-glycoprotein (P-gp) is a well-known ATP-binding cassette (ABC) transporter that plays a crucial role in the extrusion of toxic substances, decreasing their accumulation and potential intracellular effects in virtue of its broad substrate specificity, its expression in many excretory tissues and its large efflux capacity. The interaction of STXs with LA was evaluated by ab initio simulation, molecular docking and bioassays using the cell line HT-22. The interaction of STXs with LA occurs by physisorption. Molecular docking indicated that STXs can be a substrate of P-gp and, estimating the Free Energy of Binding (FEB), LA has lower amino acids residues binding sites, similar to verapamil, while STX and STX+LA_1 have similar amino acids residues and binding sites with similar FEB between this ligands.Cells were exposed to STXs and LA for 30 min and 24 hr. LA treatment minimizes STX cytotoxicity, evaluated by trypan blue and MTT assay and both STX and STX-LA treatments were efficient to induce P-gp activity measured by rhodamine 123 dye extrusion. LA and STX+LA treatments induced low reactive oxygen species levels and low oxygen consumption. Based on our results, it can be concluded that LA was able to induce cytoprotection, including induction of cellular glutathione levels, and that STX+LA interaction reduced toxicity effects induced by STX. Overall, the in vitro results corroborated the semi-empirical evidences found using density functional theory ab initio simulation and molecular docking.|Several species of crabs are resistant to paralytic shellfish toxins (PSTs) and/or pufferfish toxin, tetrodotoxin, regardless of toxification by the toxins. The shore crab Thalamita crenata, which inhabits Leizhou Peninsula, China, is tolerant to PST toxicity, and the hemolymph has neutralizing effects against the lethal activity of PST. In the present study, we investigated the PST neutralizing factors in the hemolymph from T. crenata and successfully separated PST-binding proteins by PST-ligand affinity chromatography. The neutralization factors, obtained in the fraction with a molecular weight over 10 kDa by ultrafiltration, were susceptible to proteases such as alcalase, animal complex proteases, pancreatin, and papain. The PST-binding protein had high dose-dependent neutralization effects on PST toxicity. The PST-binding activity of the protein was stable at 25 °C and then decreased with an increase in temperature; heating at 65 °C for 60 min eliminated the initial activity by two-thirds. The PST-binding activity was strongly inhibited in the presence of Mg(2+) and Ca(2+), but not Na(+) and K(+). The PST-binding capability of the protein differed among PST components in descending order of neosaxitoxin, gonyautoxins 1 and 4, saxitoxin, and gonyautoxins 2 and 3, suggesting a structure-activity relationship in PST binding.

LD50 Mouse oral 263 ug/kg|LD50 Mouse ip 10 ug/kg|LD50 Mouse iv 3400 ng/kg

/BIRDS and MAMMALS/ Paralytic shellfish poisoning (PSP) is an acute toxic illness in humans resulting from ingestion of shellfish contaminated with a suite of neurotoxins (saxitoxins) produced by marine dinoflagellates, most commonly in the genus Alexandrium. Poisoning also has been sporadically suspected and, less often, documented in marine wildlife, often in association with an outbreak in humans. Kittlitz's Murrelet (Brachyramphus brevirostris) is a small, rare seabird of the Northern Pacific with a declining population. From 2008 to 2012, as part of a breeding ecology study, multiple Kittlitz's Murrelet nests on Kodiak Island, Alaska, were monitored by remote cameras. During the 2011 and 2012 breeding seasons, nestlings from several sites died during mild weather conditions. Remote camera observations revealed that the nestlings died shortly after consuming sand lance (Ammodytes hexapterus), a fish species known to biomagnify saxitoxin. High levels of saxitoxin were subsequently documented in crop content in 87% of nestling carcasses. Marine bird deaths from PSP may be underreported.|/AQUATIC SPECIES/ Harmful Algal Blooms are worldwide occurrences that can cause poisoning in human seafood consumers as well as mortality and sublethal effets in wildlife, propagating economic losses. One of the most widespread toxigenic microalgal taxa is the dinoflagellate Genus Alexandrium, that includes species producing neurotoxins referred to as PST (Paralytic Shellfish Toxins). Blooms cause shellfish harvest restrictions to protect human consumers from accumulated toxins. Large inter-individual variability in toxin load within an exposed bivalve population complicates monitoring of shellfish toxicity for ecology and human health regulation. To decipher the physiological pathways involved in the bivalve response to PST, we explored the whole transcriptome of the digestive gland of the Pacific oyster Crassostrea gigas fed experimentally with a toxic Alexandrium minutum culture. The largest differences in transcript abundance were between oysters with contrasting toxin loads (1098 transcripts), rather than between exposed and non-exposed oysters (16 transcripts), emphasizing the importance of toxin load in oyster response to toxic dinoflagellates. Additionally, penalized regressions, innovative in this field, modeled accurately toxin load based upon only 70 transcripts. Transcriptomic differences between oysters with contrasting PST burdens revealed a limited suite of metabolic pathways affected, including ion channels, neuromuscular communication, and digestion, all of which are interconnected and linked to sodium and calcium exchanges. Carbohydrate metabolism, unconsidered previously in studies of harmful algal effects on shellfish, was also highlighted, suggesting energy challenge in oysters with high toxin loads. Associations between toxin load, genotype, and mRNA levels were revealed that open new doors for genetic studies identifying genetically-based low toxin accumulation.|/AQUATIC SPECIES/ Saxitoxins (STXs) are paralytic alkaloids produced by marine dinoflagellates in response to biotic and abiotic stressors yielding harmful algal blooms. Because STX impacts coastal, near-shore communities to a greater extent than would be predicted by its relative abundance, it has been referred to as a "molecule of keystone significance" in reference to Robert Paine's Keystone Species Concept. Pisaster ochraceus, the predator upon which Paine's concept was founded, inhabits waters regularly plagued by harmful algal blooms, but the effects of STX on Pisaster have not yet been investigated. ...Laboratory and field experiments /were used/ to examine the potential consequences of exposure to STX on sea stars' feeding, attachment to the substrate, and success in fertilization. Pisaster exhibited similar feeding behaviors when offered non-toxic prey, STX-containing prey, or a combination of the two. Although feeding behavior is unaffected, consumption of STX poses a physiological tradeoff. Sea stars in the laboratory and field had significantly lower thresholds of the force needed to detach them from their substrates after either being exposed to, or consuming, STX. High pressure (or high performance) liquid chromatography analysis indicated an accumulation of STX (and structural analogues) in sea stars' viscera, likely due to trophic transfer from toxic prey. Incidence of fertilization tended to decrease when gametes were exposed to high, yet ecologically relevant, STX concentrations of STX. These findings suggest that the molecule of keystone significance, STX, produced during harmful algal blooms extends its impacts to rocky intertidal communities by way of the keystone predator P. ochraceus.|/AQUATIC SPECIES/ The sensitivity of 8 bivalve mollusc species to tetrodotoxin roughly parallels sensitivity to saxitoxin. Resistance to the toxins was a property of the nerve fibers, and not due to the protective sheath. Sodium deficiency blocked the action potential in the resistant nerves.|For more Ecotoxicity Excerpts (Complete) data for Saxitoxin dihydrochloride (13 total), please visit the HSDB record page.

Saxitoxins are potent neurotoxins produced by cyanobacteria (blue-green algae) and dinoflagellates in both marine and freshwater environments(1). Saxitoxin and its more than 50 analogs are known as paralytic shellfish poisons. These are tricyclic alkaloid neurotoxins that permanently block voltage-gated sodium channels in nerve cells causing paralysis. These neurotoxins are distributed widely in nature, occurring in both fresh and saltwater(2). The compound is found in California mussels (Mytilus californianus), Alaska butter clams (Saxidomus giganteus), Pacific dinoflagellate (Gonyaulax catenalla), New England soft shell clams (Mya arenaria) and cultures of the Atlantic dinoflagellate (G. tamarensis)(3). It has also been reported in cockles, clams, scallops, shellfish broth(4), Australian xanthid crab and Washington clam(5). Bivalve mussels are the most common vehicles(4). The toxin is produced by several genera of plankton. Saxitoxin was rarely found in northern temperate lakes but has now been reported in the Great Lakes. The compound has been found in cyanobacterial benthic mat samples in the Arctic(2). These poisonous shellfish have been connected to instances of toxic "red-tides" where the high concentrations of algae discoloring the water were of the Gonyaulax genus(6). /Saxitoxin/|From January 2002 to May 2004, 28 puffer fish poisoning (PFP) cases in Florida, New Jersey, Virginia, and New York were linked to the Indian River Lagoon (IRL) in Florida. Saxitoxins (STXs) of unknown source were first identified in fillet remnants from a New Jersey PFP case in 2002. ... STXs /were found/ in 516 IRL southern (Sphoeroides nephelus), checkered (Sphoeroides testudineus), and bandtail (Sphoeroides spengleri) puffer fish. During 36 months of monitoring, ... STXs /were detected/ in skin, muscle, and viscera, with concentrations up to 22,104 ug STX equivalents (eq)/100 g tissue (action level, 80 ug STX eq/100 g tissue) in ovaries. Puffer fish tissues, clonal cultures, and natural bloom samples of P. bahamense from the IRL tested toxic in the MBA, RBA, MNCA, Ridascreen ELISA, and MIST Alert assay and positive for STX, dc-STX, and B1 toxin by HPLC and LC-MS. Skin mucus of IRL southern puffer fish captive for 1-year was highly toxic compared to Florida Gulf coast puffer fish. southern (Sphoeroides nephelus), checkered (Sphoeroides testudineus), and bandtail (Sphoeroides spengleri) puffer fish /were confirmed/ to be a hazardous reservoir of STXs in Florida's marine waters and implicate the dinoflagellate P. bahamense as the putative toxin source.|The dinoflagellates.../which/ produce the paralytic poison...usually bloom at latitudes greater than 30 deg north or south in areas where the water temp is around 13 deg to 18 °C. ... Investigation of the toxins of Aphanizomenon flos-aquae indicates that this alga contains three toxins in addition to saxitoxin. /Saxitoxin/

DRINKING WATER: Cyanobacteria are ubiquitous phototrophic bacteria that inhabit diverse environments across the planet. Seasonally, they dominate many eutrophic lakes impacted by excess nitrogen (N) and phosphorus (P) forming dense accumulations of biomass known as cyanobacterial harmful algal blooms or cyanoHABs. Their dominance in eutrophic lakes is attributed to a variety of unique adaptations including N and P concentrating mechanisms, N2 fixation, colony formation that inhibits predation, vertical movement via gas vesicles, and the production of toxic or otherwise bioactive molecules. While some of these molecules have been explored for their medicinal benefits, others are potent toxins harmful to humans, animals, and other wildlife known as cyanotoxins. In humans these cyanotoxins affect various tissues, including the liver, central and peripheral nervous system, kidneys, and reproductive organs among others. They induce acute effects at low doses in the parts-per-billion range and some are tumor promoters linked to chronic diseases such as liver and colorectal cancer. The occurrence of cyanoHABs and cyanotoxins in lakes presents challenges for maintaining safe recreational aquatic environments and the production of potable drinking water. CyanoHABs are a growing problem in the North American (Laurentian) Great Lakes basin. This review summarizes information on the occurrence of cyanoHABs in the Great Lakes, toxicological effects of cyanotoxins, and appropriate numerical limits on cyanotoxins in finished drinking water.|SURFACE WATER: An area of discolored water 50 m wide and 30 m long was found in September 2017 close to the dam of the Irkutsk hydroelectric power station /East Siberia, Russia/. Water from this spot was sampled for investigation in the present study. Microscopic analysis revealed that the suspended matter in the sample was composed of clumps of filaments, vegetative cells, akinetes and heterocysts that formed short filaments and solitary cells. This matter was found to consist of partially degraded cells of the cyanobacterium Dolichospermum lemmermannii. Nucleotide sequencing of DNA isolated from the biomass revealed the presence of the sxtA gene which is involved in the synthesis of saxitoxin. Water from the polluted area contained 600 ug L-1 saxitoxin as measured by HPLC-MS with pre-column modification of the toxin with 2,4-dinitrophenylhydrazine. Immunoassay analysis (ELISA) showed a concentration of saxitoxins in the water of 2900 ug L-1. Hydrochemical and microbiological analyses suggested the contaminated area appeared as a result of a D. lemmermannii bloom, followed by its decay and release of saxitoxin and nutrients. The present paper describes the results of a case study. Better understanding of the phenomenon will depend on the possibility to perform implementation of a large-scale monitoring program.|SURFACE WATER: Cyanobacteria are ubiquitous phototrophic bacteria that inhabit diverse environments across the planet. Seasonally, they dominate many eutrophic lakes impacted by excess nitrogen (N) and phosphorus (P) forming dense accumulations of biomass known as cyanobacterial harmful algal blooms or cyanoHABs. Their dominance in eutrophic lakes is attributed to a variety of unique adaptations including N and P concentrating mechanisms, N2 fixation, colony formation that inhibits predation, vertical movement via gas vesicles, and the production of toxic or otherwise bioactive molecules. While some of these molecules have been explored for their medicinal benefits, others are potent toxins harmful to humans, animals, and other wildlife known as cyanotoxins. In humans these cyanotoxins affect various tissues, including the liver, central and peripheral nervous system, kidneys, and reproductive organs among others. They induce acute effects at low doses in the parts-per-billion range and some are tumor promoters linked to chronic diseases such as liver and colorectal cancer. The occurrence of cyanoHABs and cyanotoxins in lakes presents challenges for maintaining safe recreational aquatic environments and the production of potable drinking water. CyanoHABs are a growing problem in the North American (Laurentian) Great Lakes basin. This review summarizes information on the occurrence of cyanoHABs in the Great Lakes, toxicological effects of cyanotoxins, and appropriate numerical limits on cyanotoxins in finished drinking water.|SEAWATER: Harmful algal blooms (HABs) have increased throughout the world's coastal oceans during the last century mostly due to water eutrophication and climate change. These blooms are often accompanied by extreme extensive negative impacts to fisheries, coastal resources, public health and local economies. However, limited studies have reported HAB events in Red Sea coastal waters. This article reviews potentially harmful microalgae in the Red Sea, based on available published information during the last 3 decades. Five harmful algal blooms were recorded in the Red Sea; of which 3 blooms are formed by dinoflagellates (Noctiluca scintillans, Pyrodinuium bahamense, Protoperidinium quinquecorne), one by raphidophytes (Heterosigma akashiwo) and one by cyanobacteria (Trichodesmium erythraeum). Additionally, mangrove swamps in the Red Sea were occupied by cyanobacterial mats, which contain microcystin and saxitoxin-producing species. The existing data in this review could be a catalyst for the establishment of monitoring and management program for HABs and their toxins in Red Sea coastal waters. This review also identifies current research gaps and suggests future research directions.|SEAWATER: Despite the long history of paralytic shellfish poisoning (PSP) events in Alaska, little is known about the seasonal distribution and abundance of the causative organism, Alexandrium, or the environmental factors that govern toxic bloom development. To address this issue, a five-year study (2012-2017) was undertaken in Kachemak Bay and lower Cook Inlet Alaska to determine how the occurrence of Alexandrium catenella, the dominant PSP-causing Alexandrium species, was influenced by temperature, salinity, nutrient concentrations, and other environmental factors. Cell concentrations from 572 surface water samples were estimated using quantitative PCR. Monthly sampling revealed a seasonal pattern of A. catenella bloom development that was positively correlated with water temperature. Prevailing salinity conditions did not significantly affect abundance, nor was nutrient limitation a direct factor. Elevated cell concentrations were detected in 35 samples from Kachemak Bay (100-3050 cell eq/ L) while a maximum abundance of 67 cell eq/ L was detected in samples from lower Cook Inlet sites. Monitoring data showed average water temperatures in Kachemak Bay increased by approximately 2 °C over the course of the study and were accompanied by an increase in Alexandrium abundance. Based on these findings, 7-8 °C appears to represent a temperature threshold for significant bloom development in Kachemak Bay, with the greatest risk of shellfish toxicity occurring when temperatures exceed 10-12 °C. The role of temperature is further supported by time series data from the Alaska Coastal Current (station GAK1), which showed that summertime shellfish toxicity events in Kachemak Bay generally followed periods of anomalously high winter water temperatures. These data indicate monitoring changes in water temperatures may be used as an early warning signal for subsequent development of shellfish toxicity in Kachemak Bay.

A case of an elderly female with suspected paralytic shellfish poisoning (PSP) is presented. The patient shared a meal of recreationally-harvested shellfish with her family and soon began to experience nausea and weakness. She was taken to the local emergency department and then transported to a larger hospital in Anchorage where she was admitted to the intensive care unit with respiratory depression and shock. Her condition improved, and she was discharged from the hospital 6 days later. No others who shared the meal reported symptoms of PSP. ... Urine from the patient was submitted to Centers for Disease Control for analysis of selected PSTs and creatinine. STX (64.0 ug/g-creatinine), NEO (60.0 ug/g-creatinine) and GTX1-4 (492-4780 ug/g-creatinine) were identified in the urine using online solid phase extraction with HPLC and tandem mass spectrometry. This was the first time GTX were identified in urine of a PSP case from Alaska, highlighting the need to include all STX congeners in testing to protect the public's health through a better understand of PST toxicity, monitoring and prevention of exposures.

/EXPL THER/ PURPOSE: The aim of the current study was to define the efficacy of saxitoxin as a corneal anesthetic in rabbits after mechanical corneal abrasion and photorefractive keratectomy (PRK). METHODS: Twelve Dutch belted rabbits were given a single 1.2-microg dose of saxitoxin or vehicle after mechanical abrasion of the cornea. Corneal sensation was evaluated hourly for 6 hours. A second group of 12 Dutch belted rabbits was given a 1.2-microg dose of saxitoxin or vehicle every 5 hours for 30 hours after PRK. Corneal sensation was evaluated after 5, 10, 15, 20, 25, and 30 hours. Pachometry was performed before PRK and again after the epithelial defects had healed. The rate of epithelial defect closure was assessed by measuring the epithelial defect size 25, 42, 65, 88, and 113 hours after PRK. RESULTS: A dose of 1.2 microg of saxitoxin given every 5 hours produced continuous corneal anesthesia after PRK. There was no difference in the rate of wound healing between eyes treated with saxitoxin and vehicle. There was no difference in the degree of wound healing, as measured by pachometry, between eyes treated with saxitoxin and vehicle. There were no apparent ocular or systemic toxic effects from saxitoxin administration. CONCLUSION: At a dose of 1.2 microg, saxitoxin is a safe, effective, long-acting corneal anesthetic in rabbits after PRK. /VET/|/EXPL THER/ Saxitoxin (STX) and its 57 analogs are a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs). PSTs are the causative agents of paralytic shellfish poisoning (PSP) and are mostly associated with marine dinoflagellates (eukaryotes) and freshwater cyanobacteria (prokaryotes), which form extensive blooms around the world. PST producing dinoflagellates belong to the genera Alexandrium, Gymnodinium and Pyrodinium whilst production has been identified in several cyanobacterial genera including Anabaena, Cylindrospermopsis, Aphanizomenon Planktothrix and Lyngbya. STX and its analogs can be structurally classified into several classes such as non-sulfated, mono-sulfated, di-sulfated, decarbamoylated and the recently discovered hydrophobic analogs--each with varying levels of toxicity. Biotransformation of the PSTs into other PST analogs has been identified within marine invertebrates, humans and bacteria. An improved understanding of PST transformation into less toxic analogs and degradation, both chemically or enzymatically, will be important for the development of methods for the detoxification of contaminated water supplies and of shellfish destined for consumption. Some PSTs also have demonstrated pharmaceutical potential as a long-term anesthetic in the treatment of anal fissures and for chronic tension-type headache. The recent elucidation of the saxitoxin biosynthetic gene cluster in cyanobacteria and the identification of new PST analogs will present opportunities to further explore the pharmaceutical potential of these intriguing alkaloids.|/EXPL THER/ Both chronic and neuropathic pain conditions are associated with increased expression of certain voltage-gated sodium ion channel (NaV) isoforms in peripheral sensory neurons. A method for noninvasive imaging of these channels could represent a powerful tool for investigating aberrant expression of NaV and its role in pain pathogenesis. Herein, we describe the synthesis and evaluation of a positron emission tomography (PET) radiotracer targeting NaVs, the design of which is based on the potent, NaV-selective inhibitor saxitoxin. Both autoradiography analysis of sciatic nerves excised from injured rats as well as whole animal PET-MR imaging demonstrate that a systemically administered [(18)F]-labeled saxitoxin derivative concentrates at the site of nerve injury, consistent with upregulated sodium channel expression following axotomy. This type of PET agent has potential use for serial monitoring of channel expression levels at injured nerves throughout wound healing and/or following drug treatment. Such information may be correlated with pain behavioral analyses to help shed light on the complex molecular processes that underlie pain sensation.

Algae dietary supplements are marketed worldwide as natural health products. Although their proprieties have been claimed as beneficial to improve overall health, there have been several previous reports of contamination by cyanotoxins. These products generally contain non-toxic cyanobacteria, but the methods of cultivation in natural waters without appropriate quality controls allow contamination by toxin producer species present in the natural environment. In this study, we investigated the presence of total microcystins, seven individual microcystins (RR, YR, LR, LA, LY, LW, LF), anatoxin-a, dihydroanatoxin-a, epoxyanatoxin-a, cylindrospermopsin, saxitoxin, and beta-methylamino-l-alanine in 18 different commercially available products containing Spirulina or Aphanizomenon flos-aquae. Total microcystins analysis was accomplished using a Lemieux oxidation and a chemical derivatization using dansyl chloride was needed for the simultaneous analysis of cylindrospermopsin, saxitoxin, and beta-methylamino-l-alanine. Moreover, the use of laser diode thermal desorption (LDTD) and ultra-high performance liquid chromatography (UHPLC) both coupled to high resolution mass spectrometry (HRMS) enabled high performance detection and quantitation. Out of the 18 products analyzed, 8 contained some cyanotoxins at levels exceeding the tolerable daily intake values. The presence of cyanotoxins in these algal dietary supplements reinforces the need for a better quality control as well as consumer's awareness on the potential risks associated with the consumption of these supplements.

Moderate symptoms are produced by 120 to 180 ug/person and are reversible within hours or days, whereas 80 ug of purified toxin per 100 g of tissue (0.5-2 mg/person) may be lethal, due to asphyxiation, usually within 12 hours of ingestion.

Toxic materials are stored in various parts of the body of shellfish. Digestive organs, liver, gills, and siphons contain the greatest concentrations of poison during the warmer months.|The disposition of STX in Atlantic salmon (Salmo salar) and Atlantic cod (Gadus morhua) was studied after intraperitoneal (IP) injection (5 microg STX/kg bm and 3.43 microg (3)H-STXeq/kg bw respectively), intravenous (IV) injection (5 microg STX/kg bm, only salmon) and waterborne exposure (50 microg STXeq/L, only salmon). Plasma concentrations in salmon were quantified using a receptor binding assay and cod tissues were analyzed using scintillation counting of tissue extracts and autoradiography of whole fish slices. The estimated elimination half-life (T(1/2)) after IV administration of STX in salmon was 102.6 min. The volume of distribution (Vz) was observed to be 467.2 mL/kg and the total body clearance (Cl(T)) was 3.2 mL/min/kg. Waterborne exposure clearly showed that salmon absorbed PSP toxins directly from the water. In cod, (3)H-STX was observed in gills, muscle, brain, liver and posterior kidney from 30 to 480 min. The lowest concentrations of (3)H-STX were found in brain and muscle, whereas posterior kidney contained the majority of the toxin. Autoradiograms confirmed the high levels of (3)H-STX in the kidneys, indicating that renal excretion was the main elimination route. Buildup of harmful levels in edible tissue is not very likely due to the low concentrations accumulated in muscle tissue and rapid excretion.|Saxitoxin (STX) is one of several related toxins that cause paralytic shellfish poisoning (PSP). This toxin blocks neuronal transmission by binding to the voltage-gated Na+ channel and for this reason, it has been widely used in the study of Na+ channel. The aim of this study was to analyze STX distribution in different rat brain regions after its acute intraperitoneal (i.p.) administration. Male rats (150-200 g) were injected i.p. with STX (5 and 10 ug/kg of body weight). After three time intervals of 30, 60, and 120 min (for 5 ug/kg STX dose) and 30 min (for 10 ug/kg STX dose) animals were sacrificed by cervical dislocation. Brains were removed and dissected in seven regions. STX concentration was measured using a precolumn oxidation high-performance liquid chromatographic method with fluorescence detection (HPLC/FLD). STX was found in all the regions evaluated at ppm levels meaning that STX peripherical administered across the blood-brain barrier and is distributed along the whole brain.|BACKGROUND: From January 2002 to May 2004, 28 puffer fish poisoning (PFP) cases in Florida, New Jersey, Virginia, and New York were linked to the Indian River Lagoon (IRL) in Florida. Saxitoxins (STXs) of unknown source were first identified in fillet remnants from a New Jersey PFP case in 2002. METHODS: We used the standard mouse bioassay (MBA), receptor binding assay (RBA), mouse neuroblastoma cytotoxicity assay (MNCA), Ridascreen ELISA, MIST Alert assay, HPLC, and liquid chromatography-mass spectrometry (LC-MS) to determine the presence of STX, decarbamoyl STX (dc-STX), and N-sulfocarbamoyl (B1) toxin in puffer fish tissues, clonal cultures, and natural bloom samples of Pyrodinium bahamense from the IRL. RESULTS: We found STXs in 516 IRL southern (Sphoeroides nephelus), checkered (Sphoeroides testudineus), and bandtail (Sphoeroides spengleri) puffer fish. During 36 months of monitoring, we detected STXs in skin, muscle, and viscera, with concentrations up to 22,104 ug STX equivalents (eq)/100 g tissue (action level, 80 ug STX eq/100 g tissue) in ovaries. Puffer fish tissues, clonal cultures, and natural bloom samples of P. bahamense from the IRL tested toxic in the MBA, RBA, MNCA, Ridascreen ELISA, and MIST Alert assay and positive for STX, dc-STX, and B1 toxin by HPLC and LC-MS. Skin mucus of IRL southern puffer fish captive for 1-year was highly toxic compared to Florida Gulf coast puffer fish. Therefore, we confirm puffer fish to be a hazardous reservoir of STXs in Florida's marine waters and implicate the dinoflagellate P. bahamense as the putative toxin source. CONCLUSIONS: Associated with fatal paralytic shellfish poisoning (PSP) in the Pacific but not known to be toxic in the western Atlantic, P. bahamense is an emerging public health threat. We propose characterizing this food poisoning syndrome as saxitoxin puffer fish poisoning (SPFP) to distinguish it from PFP, which is traditionally associated with tetrodotoxin, and from PSP caused by STXs in shellfish.

Bivalve metabolites of saxitoxin analogues, not present in microalgae, were recently described as an important toxin fraction in mussels contaminated by Alexandrium tamarense. These possess very low fluorescence, and require mass spectrometry detection. HILIC-MS was implemented to look for these metabolites in bivalves contaminated during Gymnodinium catenatum blooms at the Portuguese coast. The presence of M1 was tentatively identified in several bivalves, ranging from estuarine (Mytilus galloprovinciallis, Cerastoderma edule and Ruditapes decussatus) to oceanic habitat (Donax trunculus and Ensis spp.). It was hypothesized that M1 could contribute to an important fraction of the profile of STX analogues. M1 was more abundant in estuarine bivalves that retain longer PSP toxins, in the following order: mussels>cockles>clams. These data highlight that the study by fluorimetry alone of the carbamoyl, N-sulfocarbamoyl, and decarbamoyl families is manifestly insufficient to fully understand toxin dynamics in bivalves feeding on G. catenatum without a proper study of hydroxybenzoate and hydroxylated M-toxins.

The estimated elimination half-life (T(1/2)) after IV administration of STX in salmon was 102.6 min.

Saxitoxin, originally isolated from toxic Alaskan butter clams (Saxidomus giganteus) is actually a family of neurotoxins and includes nesaxitin and gonyautoxin one through four. All block neural transmission at the neuromuscular junction by binding to the surface of the sodium channels and interrupting the flow of Na+ ions; apical vesicles (AV) nodal conduction may be suppressed, there may be direct suppression of respiratory cernter and progressive reduction of peripheral nerve excitability.|Marine neurotoxins are natural products produced by phytoplankton and select species of invertebrates and fish. These compounds interact with voltage-gated sodium, potassium and calcium channels and modulate the flux of these ions into various cell types. This review provides a summary of marine neurotoxins, including their structures, molecular targets and pharmacologies. Saxitoxin and its derivatives, collectively referred to as paralytic shellfish toxins (PSTs), are unique among neurotoxins in that they are found in both marine and freshwater environments by organisms inhabiting two kingdoms of life. Prokaryotic cyanobacteria are responsible for PST production in freshwater systems, while eukaryotic dinoflagellates are the main producers in marine waters. Bioaccumulation by filter-feeding bivalves and fish and subsequent transfer through the food web results in the potentially fatal human illnesses, paralytic shellfish poisoning and saxitoxin pufferfish poisoning. These illnesses are a result of saxitoxin's ability to bind to the voltage-gated sodium channel, blocking the passage of nerve impulses and leading to death via respiratory paralysis. Recent advances in saxitoxin research are discussed, including the molecular biology of toxin synthesis, new protein targets, association with metal-binding motifs and methods of detection. The eco-evolutionary role(s) PSTs may serve for phytoplankton species that produce them are also discussed.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ Saxitoxin produces paresthesia and neuromuscular weakness without hypotension and lacks the emetic and hypothermic action of tetrodotoxin. Moderate symptoms are produced by 120 to 180 ug/person and are reversible within hours or days, whereas 80 ug of purified toxin per 100 g of tissue (0.5-2 mg/person) may be lethal, due to asphyxiation, usually within 12 hours of ingestion.|/SIGNS AND SYMPTOMS/ Exposure to saxitoxin most commonly occurs following ingestion of certain fish that contain it in their tissues. Ingestion of saxitoxin can cause numbness of the oral mucosa as quickly as 30 minutes after exposure. In severe poisoning, illness typically progresses rapidly and may include gastrointestinal (nausea, vomiting) and neurological (cranial nerve dysfunction, a floating sensation, headache, muscle weakness, parasthesias and vertigo) signs and symptoms. Respiratory failure and death can occur from paralysis.|/CASE REPORTS/ A case of an elderly female with suspected paralytic shellfish poisoning (PSP) is presented. The patient shared a meal of recreationally-harvested shellfish with her family and soon began to experience nausea and weakness. She was taken to the local emergency department and then transported to a larger hospital in Anchorage where she was admitted to the intensive care unit with respiratory depression and shock. Her condition improved, and she was discharged from the hospital 6 days later. No others who shared the meal reported symptoms of PSP. A clam remaining from the meal was collected and analyzed for paralytic shellfish toxins (PST) by the Alaska Department of Environmental Conservation Environmental Health Laboratory; the clam tested positive for saxitoxin (STX; 277 ug/100 g), neosaxitoxin (NEO; 309 ug/100 g), multiple gonyautoxins (GTX; 576-2490 ug/100 g), decarbamoyl congeners (7.52-11.3 ug/100 g) and C-toxins (10.8-221 ug/100 g) using high-pressure liquid chromatography with post-column oxidation (AOAC Method 2011.02). Urine from the patient was submitted to Centers for Disease Control for analysis of selected PSTs and creatinine. STX (64.0 ug/g-creatinine), NEO (60.0 ug/g-creatinine) and GTX1-4 (492-4780 ug/g-creatinine) were identified in the urine using online solid phase extraction with HPLC and tandem mass spectrometry. This was the first time GTX were identified in urine of a PSP case from Alaska, highlighting the need to include all STX congeners in testing to protect the public's health through a better understand of PST toxicity, monitoring and prevention of exposures.|/CASE REPORTS/ During the months of January-February and May-June 2013 coinciding with the red tide occurrence in Kota Kinabalu, Sabah, Malaysia, six episodes involving 58 cases of paralytic shellfish poisoning (PSP) or saxitoxin (STX) poisoning and resulting in four deaths were reported. Many of them were intoxicated from consuming shellfish purchased from the markets, whereas others were intoxicated from eating shellfish collected from the beach. Levels of STX in shellfish collected from the affected areas were high (mean 2,920 +/- 780 and 360 +/- 140 ug STX equivalents/100 g shellfish meat respectively for the two periods). The count of toxic dinoflagellates (Pyrodinium bahamense var compressum) of the sea water sampled around the coast was also high (mean 34,200 +/- 10,300 cells/L). Species of shellfish containing high levels of STX were Atrina fragilis, Perna viridis, and Crassostrea belcheri. The age of victims varied from 9 to 67 years. Symptoms presented were typical of PSP, such as dizziness, numbness, vomiting, and difficulty in breathing. Recommended steps to prevent or reduce PSP in future red tide season include better monitoring of red tide occurrence, regular sampling of shellfish for determination of STX level, wider dissemination of information on the danger of eating contaminated shellfish among the communities, fishermen, and fishmongers.|For more Human Toxicity Excerpts (Complete) data for Saxitoxin dihydrochloride (13 total), please visit the HSDB record page.

STX /saxitoxin/ is listed in schedule 1 of the Chemical Weapons Convention (CWC). /Saxitoxin/|A toxic principle present in certain species of shellfish. It is a paralytic poison that attacks the central nervous system, acting as a muscular nerve block. /Saxitoxin/|The toxin is an alkaloid and is relatively heat-stable.|Toxic materials are stored in various parts of the body of shellfish. Digestive organs, liver, gills, and siphons contain the greatest concentrations of poison during the warmer months.

In this study, a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for simultaneous determination of eight paralytic shellfish poisoning (PSP) toxins, including saxitoxin (STX), neosaxitoxin (NEO), gonyautoxins (GTX1-4) and the N-sulfo carbamoyl toxins C1 and C2, in sea shellfish. The samples were extracted by acetonitrile/water (80:20, v/v) with 0.1% formic and purified by dispersive solid-phase extraction (dSPE) with C18 silica and acidic alumina. Qualitative and quantitative detection for the target toxins were conducted under the multiple reaction monitoring (MRM) mode by using the positive electrospray ionization (ESI) mode after chromatographic separation on a TSK-gel Amide-80 HILIC column with water and acetonitrile. Matrix-matched calibration was used to compensate for matrix effects. The established method was further validated by determining the linearity (R(2) = 0.9900), average recovery (81.52-116.50%), sensitivity (limits of detection (LODs): 0.33-5.52 ug/kg; limits of quantitation (LOQs): 1.32-11.29 ug/kg) and precision (relative standard deviation (RSD) = 19.10%). The application of this proposed approach to thirty shellfish samples proved its desirable performance and sufficient capability for simultaneous determination of multiclass PSP toxins in sea foods.|As one of paralytic shellfish toxins, the saxitoxin (STX) in the aqueous environment can be accumulated by most shellfish, and thus harms human health through the food chain. Therefore, it is crucial to determine trace STX in seafood samples in order to ensure the safety of seafood consumption. In this study, we developed a novel indirect method for ultrasensitively determining trace STX in seafood by using CE-ICP-MS together with Eu3+ chelate labeling. We demonstrated that diethylenetriamine-N,N,N',N?,N?-pentaacetic acid (DTPA) can couple with STX and simultaneously chelate with Eu3+ to realize metallic labeling of STX, and thus realize the ultrasensitive quantification of trace STX with CE-ICP-MS. The proposed method has strong antiinterference ability, good stability, and extremely high sensitivity. It could be used to determine trace STX in seafood samples with an extremely low detection limit of 0.38 fmol (3.8x10-9 M, 100 nL sample injection) and a relative standard deviation (RSD, n = 5) <7%. The success of this study provides an alternative to precise quantification of ultra-trace STX in seafood samples, and further expands the application of ICP-MS.|Hydrophilic-interaction chromatography (HILIC) is reportedly useful for the analysis of saxitoxin (STX) analogues, collectively known as paralytic shellfish toxins. Column switching and two-step gradient elution using HILIC combined with mass spectrometry enabled the simultaneous analysis of the 15 primary STX analogues and their biosynthetic intermediates, arginine, Int-A', and Int-C'2, and the shunt product, Cyclic-C'. Crude extracts of toxin-producing dinoflagellates can be injected without any treatment except filtration. Enrichment of the compounds using this method was highly reproducible with respect to retention times (% RSD was under 1%) and highly sensitive (limits of detection (LODs) were in the range 0.9 (Int-C'2) - 116 (C3) uM) in terms of avoiding matrix effects associated with co-eluting substances. Validation studies demonstrated acceptable performance of this method for specificity, repeatability, linearity and recovery. A comparison of the quantitative results for STX analogues in Alexandrium tamarense using HPLC with post-column fluorescent derivatization and the column-switching HILIC-MS method revealed good agreement. The presence of Int-A', Int-C'2, and Cyclic-C' in toxic dinoflagellate species with different toxin profiles was confirmed using this method. Our data support the hypothesis that the early stages of the STX biosynthesis and shunt pathways are the same in dinoflagellates and cyanobacteria.|Paralytic shellfish poisoning (PSP) is a serious human illness caused by the ingestion of seafood contaminated with saxitoxin and its derivatives (STXs). These toxins are produced by some species of marine dinoflagellates within the genus Alexandrium. In the Mediterranean Sea, toxic Alexandrium spp. blooms, especially of A. minutum, are frequent and intense with negative impact to coastal ecosystem, aquaculture practices and other economic activities. We conducted a large scale study on the sxt gene and toxin distribution and content in toxic dinoflagellate A. minutum of the Mediterranean Sea using both quantitative PCR (qPCR) and HILIC-HRMS techniques. We developed a new qPCR assay for the estimation of the sxtA1 gene copy number in seawater samples during a bloom event in Syracuse Bay (Mediterranean Sea) with an analytical sensitivity of 2.0 x 10(0) sxtA1 gene copy number per reaction. The linear correlation between sxtA1 gene copy number and microalgal abundance and between the sxtA1 gene and STX content allowed us to rapidly determine the STX-producing cell concentrations of two Alexandrium species in environmental samples. In these samples, the amount of sxtA1 gene was in the range of 1.38 x 10(5) - 2.55 x 10(8) copies/L and the STX concentrations ranged from 41-201 nmol/L. This study described a potential PSP scenario in the Mediterranean Sea.|For more Analytic Laboratory Methods (Complete) data for Saxitoxin dihydrochloride (22 total), please visit the HSDB record page.

Saxitoxin (STX) and neosaxitoxin (NEO) are water-soluble toxins and their cleanup in bio-matrix is a hot topic but difficult problem. A fast and quantitative determination method for STX and NEO in urine was developed using ultra performance liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) based on the cleanup of solid phase extraction (SPE) with hydrophilic interaction (HILIC) mechanism. Acetonitrile/methanol/water mixture was used to extract the toxins in urine. Polyamide (PA) was used as HILIC SPE material to clean the toxins in sample matrix. The limits of detection were 0.2 ng/mL for STX and 1 ng/mL for NEO in urine. The linear ranges were 0.5-99.2 ng/mL with the correlation coefficient of r=0.9992 for STX and 2.1-207 ng/mL with r=0.997 for NEO in urine matrix. The recoveries at three spiking levels were 81.5%-117% with the relative standard deviations (RSDs) of 5.4%-8.5% for STX and 89.0%-118% with the RSDs of 6.7%-9.1% for NEO. STX was found in all the 6 patients' urines while NEO was only found in one sample from an intoxication case.|AIM: An immunomagnetic capture protocol for use with LC-MS was developed for the quantitation of saxitoxin (STX) in human urine. MATERIALS & METHODS: This method uses monoclonal antibodies coupled to magnetic beads. STX was certified reference material grade from National Research Council, Canada. Analysis was carried out using LC-MS. RESULTS: With an extraction efficiency of 80%, accuracy and precision of 93.0-100.2% and 5.3-12.6%, respectively, and a dynamic range of 1.00-100 ng/mL, the method is well suited to quantify STX exposures based on previously reported cases. CONCLUSION: Compared with our previously published protocols, this method has improved selectivity, a fivefold increase in sensitivity and uses only a third of the sample volume. This method can diagnose future toxin exposures and may complement the shellfish monitoring programs worldwide.|Saxitoxin (STX) is a potent marine toxin that causes paralytic shellfish poisoning (PSP) which can result in significant morbidity and mortality in humans. Low lethal doses, rapid onset of PSP symptoms, and brief STX half-life in vivo require sensitive and rapid diagnostic techniques to monitor human exposures. Our laboratory has validated an enzyme-linked immunosorbent assay (ELISA) for quantitative detection of STX from 0.020 to 0.80 ng/mL in human whole blood and from 0.06 to 2.0 ng/mL in dried human blood which is simple, sensitive, rapid, and cost-effective. To our knowledge, this is the first validated method for the quantitation of saxitoxin in whole blood. Microsampling devices were used in sample collection which allows for standardized collection of blood, stable storage, and cost-efficient shipping. Quality control precision and accuracy were evaluated over the course of validation and were within 20% of theoretical concentrations. No detectable background concentrations of STX were found among fifty whole blood and dried blood convenience samples. Additionally, ten spiked individual whole blood and dried blood samples were tested for accuracy and precision and were within 20% of theoretical concentrations. Gonyautoxins 2&3 (GTX2&3) cross-reacted with this ELISA by 21%, but all other structurally related PSP toxins tested cross-reacted less than two percent. While clinical diagnosis or treatment of PSP would be unaffected by GTX2&3 cross-reactivity by ELISA, to accurately quantify individual PSP toxins, these results should be coupled with high performance liquid chromatography mass spectrometry measurements.|Saxitoxin (STX) and neosaxitoxin (NEO) are potent neurotoxins that cause paralytic shellfish poisoning (PSP). PSP typically occurs through the ingestion of bivalve shellfish that have consumed toxin producing dinoflagellates. Due to initial presentation of symptoms being nonspecific, a clinical measurement is needed to confirm exposure to these toxins. Our group has developed an online solid phase extraction hydrophilic interaction liquid chromatography (HILIC) method for the analysis of STX and NEO in human urine with tandem mass spectrometry. A unique feature of this online method is the incorporation of a new synthetic (15)N4-STX labeled internal standard used for quantitation. Manual sample preparation time was reduced by approximately 70% for 98 urine samples as compared to a previously reported method. The lowest reportable limit for STX was improved from 5.0 ng/mL to 1.01 ng/mL and from 10.0 ng/mL to 2.62 ng/mL for NEO. Three analysts validated the method with 20 calibration curves total over 30 days with precision and accuracy within +/-15% for all QCs. This new online method rapidly identifies STX and NEO exposure with improved sensitivity, which can facilitate the work of public health authorities to confirm the cases of PSP, complementing the many shellfish monitoring programs worldwide.|Saxitoxin and neosaxitoxin are potent neurotoxins that can cause paralytic shellfish poisoning when consumed. A new assay is presented here to quantify saxitoxin (STX) and neosaxitoxin (NEO) in human urine samples. Sample preparation of 500-microL samples included the use of weak-cation-exchange solid-phase extraction in a multiplexed 96-well format. Extracts were preconcentrated and analyzed via 10-min hydrophilic interaction liquid chromatography followed by electrospray ionization. Protonated molecular ions were quantified via multiple reaction monitoring mode in a Qtrap mass spectrometer. The method uses novel (15)N7-isotopically enriched STX and NEO internal standards. Method validation included the characterization of two enriched urine pools. The lowest reportable limits for STX and NEO were 4.80 and 10.1 ng/mL, respectively, using both quantification and confirmation ions. These two toxins were not detected in a reference range of humans who consumed seafood in the preceding 72 hr, suggesting that few false positives would occur when trying to identify people exposed to STX or NEO.