Development and validation of a high-throughput online solid phase extraction – Liquid chromatography – Tandem mass spectrometry method for the detection of tetrodotoxin in human urine

Abstract

Tetrodotoxin (TTX) is an extremely potent paralytic toxin responsible for yearly illness and death around the world. A clinical measurement is necessary to confirm exposure because symptoms of TTX intoxication cannot be distinguished from other paralytic toxins. Our group has developed an online solid phase extraction hydrophilic interaction liquid chromatography (HILIC) method for the analysis of TTX in human urine with tandem mass spectrometry. The reportable range for the method was 2.80 - 249 ng/mL in urine with precision and accuracy within 15% as determined for all quality control samples. No isotopically-labeled internal standard is available for TTX; thus a surrogate internal standard, voglibose, was investigated to compensate for matrix effects and ionization suppression. However, upon evaluation, voglibose was ineffective for this purpose. This new online method rapidly identifies TTX, facilitating the work of public health authorities and providing support to monitoring programs worldwide.

Simultaneous Determination of Tetrodotoxin in the Fresh and Heat-Processed Aquatic Products by High-Performance Liquid Chromatography–Tandem Mass Spectrometry

“…Figure S1 shows the total ion chromatogram (TIC) and the selective product ions chromatograms of TTX with a concentration of 25 ng/mL. The results indicated that the appropriate product ions of TTX were 320.2 > 302.2 m / z ((corresponding to a loss of water, C 11 H 15 N 3 O 7 ), 320.2 > 162.2 m / z (C 9 H 8 N 3 O), and 320.2 > 284.2 m / z (C 11 H 14 N 3 O 6 ), which were consistent with those reported in the previous studies [ 41 , 42 ]. Moreover, among the three identified product ions, 320.2 > 302.2 m / z displayed the considerable superiority, which was considered as the quantitative ion during the determination of TTX for its high intensity.…”

Chronic In Vivo Effects of Repeated Exposure to Low Oral Doses of Tetrodotoxin: Preliminary Evidence of Nephrotoxicity and Cardiotoxicity

“…Urinary excretion of TTX has been documented in humans and rats [ 23 , 27 ]. The results presented here indicate that repeated exposure of mice to TTX at doses of 75 and 125 µg/kg severely decreased urine production, which could be indicative of kidney injury.…”

Tetrodotoxin and Its Analogues in Food: Recent Updates on Sample Preparation and Analytical Methods Since 2012

“…Typically, pretreatment methods for TTXs can be divided into two parts: an extraction method and a purification method. Nevertheless, some techniques can extract target analytes and remove interfering substances simultaneously . Also, some approaches integrate extraction, purification, and preconcentration into a step. , Hence, we categorize existing pretreatment methods into several groups according to their technical characteristics and advances, which mainly include solid–liquid extraction, liquid–liquid extraction-based methods, and solid-phase extraction-based methods.…”