Development and validation of a specific and sensitive liquid chromatography tandem mass spectrometry method for determination of tetrodotoxin in human urine and its pharmacokinetic study.


Journal

Biomedical chromatography : BMC
ISSN: 1099-0801
Titre abrégé: Biomed Chromatogr
Pays: England
ID NLM: 8610241

Informations de publication

Date de publication:
Sep 2020
Historique:
received: 26 02 2020
revised: 13 05 2020
accepted: 14 05 2020
pubmed: 20 5 2020
medline: 1 4 2021
entrez: 20 5 2020
Statut: ppublish

Résumé

Tetrodotoxin (TTX) exhibits the therapeutic potential in blocking pain and in low doses can safely relieve severe pain. The urinary excretion profiles of TTX in humans have not been reported due to the extremely low lethal dose. In this study, a rapid and specific method based on protein precipitation coupled to liquid chromatography tandem mass spectrometry was developed to determine the level of TTX in human urine samples. 11-Deoxytetrodotoxin was used as an internal standard (IS). Multiple reaction monitoring mode was used for quantification using target fragment ions m/z 320.0 → 162.1 for TTX and m/z 304.0 → 176.0 for 11-deoxyTTX. The separation of analytes was achieved on a hydrophilic interaction liquid chromatography column (250 × 4.6 mm, 5.0 μm). The mobile phase consisted of 5 mM ammonium formate in water (pH = 4.50) and 5 mM ammonium formate in acetonitrile (pH = 4.50). The flow rate was set at 0.80 mL/min in a gradient condition. Calibration plots were linear throughout the range 0.986-98.6 ng/mL of TTX in human urine. The intra-assay accuracies and precisions were within the acceptable range. The method was successfully applied to a urinary excretion study after intravenous administration of TTX to healthy volunteers. The developed method will be helpful for future pharmacological studies of TTX.

Identifiants

pubmed: 32428255
doi: 10.1002/bmc.4900
doi:

Substances chimiques

11-deoxytetrodotoxin 113564-23-1
Tetrodotoxin 4368-28-9

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e4900

Subventions

Organisme : Project of Xiamen Southern Oceanographic Center, China
ID : 16PFW008SF15
Organisme : Fujian Science and Technology Key Project of China
ID : 2019N0032
Organisme : Marine Economy Innovation Develepment Area Demonstration Project of Beihai
ID : Bhsfs009
Organisme : National Key Research and Development Program of China
ID : 2016YFF0201104

Informations de copyright

© 2020 John Wiley & Sons, Ltd.

Références

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Auteurs

Weizhu Chen (W)

Third Institute of Oceanography, Ministry of Natural Resource, Xiamen, China.
Engineering Research Center of Marine Biological Resource Comprehensive Utilization, Ministry of Natural Resource, Xiamen, China.
Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological, Xiamen, China.

Yiping Zhang (Y)

Third Institute of Oceanography, Ministry of Natural Resource, Xiamen, China.
Engineering Research Center of Marine Biological Resource Comprehensive Utilization, Ministry of Natural Resource, Xiamen, China.
Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological, Xiamen, China.

Hua Fang (H)

Third Institute of Oceanography, Ministry of Natural Resource, Xiamen, China.
Engineering Research Center of Marine Biological Resource Comprehensive Utilization, Ministry of Natural Resource, Xiamen, China.
Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological, Xiamen, China.

Hui Chen (H)

Third Institute of Oceanography, Ministry of Natural Resource, Xiamen, China.
Engineering Research Center of Marine Biological Resource Comprehensive Utilization, Ministry of Natural Resource, Xiamen, China.
Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological, Xiamen, China.

Jianlin He (J)

Third Institute of Oceanography, Ministry of Natural Resource, Xiamen, China.
Engineering Research Center of Marine Biological Resource Comprehensive Utilization, Ministry of Natural Resource, Xiamen, China.
Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological, Xiamen, China.

Ruizao Yi (R)

Third Institute of Oceanography, Ministry of Natural Resource, Xiamen, China.
Engineering Research Center of Marine Biological Resource Comprehensive Utilization, Ministry of Natural Resource, Xiamen, China.
Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological, Xiamen, China.

Zhuan Hong (Z)

Third Institute of Oceanography, Ministry of Natural Resource, Xiamen, China.
Engineering Research Center of Marine Biological Resource Comprehensive Utilization, Ministry of Natural Resource, Xiamen, China.
Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological, Xiamen, China.

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