Simple and fast determination of tetrodotoxin in human plasma based on hydrophilic-interaction/ion-exchange mixed-mode solid phase extraction combined with liquid chromatography-tandem mass spectroscopy

•A fast SPE-LC/MS/MS method to detect tetrodotoxin in human plasma (<30 min).•A superior HILIC-ion exchange mixed-mode SPE was chosen after comparing three SPEs.•Evaporation and ultrafiltration steps were avoided.•The LLOQ (S/N>10) of tetrodotoxin in human plasma is as low as 0.1 ng/mL.