Objective A DART-HRMS method was developed for the rapid detection of gamma-hydroxybutyric acid and fluoroacetate in suspect samples. Methods According to the morphology of the samples, direct injection or injection after aqueous solution immersion was adopted. 12 Dip-it Samplers was used for injection. The instrument parameter were optimized to obtain the sensitive and accurate determination for GHB and fluoroacetate.In the negative ion mode , high intensity of [M-H]- ions were observed in Full MS mode with the sample introduction rate of 0.4 mm/s and by utilization of high purityhelium gas at 400 ℃. Results That the LODs of GHB in water, cola, iced tea and milk were 0.1, 0.5, 0.5 , 0.1μg/mL respectively. The LODs of fluoroacetate in water, vinegar, soy sauce and rapeseed oil were 0.01, 2, 2, 0.1μg/mL separately. This could meet the requirements of forensic science laboratory for the detection of the non-biological samples. This screening method would show its outstanding advantages including fast response, high-throughput potential to detect GHB and fluoroacetate in suspected samples. Conclusion Local forensic laboratory we reanalyzed to testify the utility of the method. In the cases with complex and diverse samples, the positive and negative samples could be quickly identified, which could also provide a reference for the pre-treatment steps and prevent the high concentration samples contaminating the GC-MS or LC-MS instruments.