LC/MS methodology for the analysis of domoic acid and lipophilic toxins in shellfish was developed using a hybrid triple quadrupole linear ion trap mass spectrometer. For routine quantitation a scheduled selected reaction monitoring (SRM) method for the analysis of domoic acid, okadaic acid, dinophysistoxins, azaspiracids, pectenotoxins, yessotoxins, gymnodimines, spirolides, and pinnatoxins was developed and validated. The method performed well in terms of LOD, linearity, precision, and trueness. Taking advantage of the high instrument sensitivity, matrix effects were mitigated by reducing the amount of sample introduced to the mass spectrometer. Optionally, samples can be analyzed using information dependent acquisition (IDA) methods, either in positive or negative mode, which can provide an extra level of confirmation by matching the full product ion spectra acquired for a sample with those from a specially constructed spectral library. Methods were applied to the analysis df a new certified reference material and Canadian mussels (Mytilus edulis) implicated in a 2011 diarrhetic shellfish poisoning (DSP) incident. The scheduled SRM method enabled the screening and quantitation of multiple phycotoxins. As DSP had not previously been observed in this area of Canada, positive identification of putative toxins was accomplished using the IDA and spectral search method. Analysis of the 2011 toxic mussel samples revealed the presence of high levels of dinophysistoxin-1, which explained the DSP symptoms, as well as pectenotoxins, yessotoxins, and variety of cyclic imines.