Saxitoxin and its analogues also called paralytic shellfish poisons (PSPs) are very potent neurotoxins [1] produced by dinoflagellates and referenced as chemical weapon in the chemical warfare convention (CWC). The official detection methods for these toxins present limitations concerning their speed and reliability [2]. Due to the presence of isomers, not differentiable by mass spectrometry (MS), an upstream separation is necessary. In order to separate saxitoxin analogues, hydrophilic interaction liquid chromatography (HILIC) and ion mobility (IM) were used. Those techniques respectively developed for high polar compounds and three dimensional structure differentiation are particularly well adapted to the separation of PSPs. This HILIC/IM-MS coupling was used to develop a fast, reproducible and sensitive method for the separation and the detection of the PSPs