BACKGROUND: Amnesic shellfish poisoning(ASP) is caused by consumption of seafood contaminated by marine neurotoxins, mainly domoic acid (DA).OBJECTIVE: To ensure the safety of shellfish consumption by determining DA in shellfish by means of liquid chromatography(LC) combined with quadrupole time-of-flight mass spectrometry(Q-TOF MS).DESIGN: A self-controlled prospective study SETTING: The experiment was carried out in the Center for Animal, Plant and Food Inspection and Quarantine, Shanghai Exit-Entry Inspection and Quarantine Bureau.MATERIALS: MUS-1B, a nominal sample of homogenized mussel tissue (containing 36 ± 1μg DA per gram, Batch No. MUS-1B 0159) and the standard DA solution (100 mg/L, Batch No. DACS-1C 352) were purchased from National Research Council of Canada (Halifax, Canada). Positive musscl samples were collected from the waters during the occurrence of red tide in China East Sea, and blank mussel samples were obtained from local seafood market. LC system (Waters 2695) combined with Q-TOF MS (Qultima, Micromass) and ultravilet (UV) detection (Waters 2487 ) was employed for analysis of ASP toxins.METHODS: The shellfish tissue samples were extracted with methanol-water (1: 1, V/V) and cleansed with a SAX solid-phase extraction cartridge. Separation was carried out on a Zorbax Eclipse XDB-18 column (250×2.1 mm, 3.5μm) with gradient elution of CAN-H20 containing 0.05% formic acid at a flow rate of 0.20 mL per minute. In a positive electrospray ionization DA was ionized effectively, and collision-induced dissociation(CID) produced predominant characteristic ions[M + H] +allowing sensitive TOF MS detection.MAIN OUTCOME MEASURES: ① Limit of quantification(LOQ); ②Accuracy and precision of LC/Q-TOF MS method.RESULTS: The average recoveries of DA spiked to tissue homogenates through the complete cleanse procedure ranged from 87.8% to 94.6%, and the relative standard deviations(RSD) ranged from 8.4% to 11.9%. TheLOQ in the shellfish tissue was 0.1 μg/g.CONCLUSION: LC/Q-TOF MS suits well the purpose of detecting and identifying ASP toxins in shellfish with high sensitivity and specificity, and may provide reference values for monitoring the safety of consumption of shellfish.