:The development of multi-analyte methods for lipophilic shellfish toxins based on liquid chromatography-mass spectrometry permits rapid screening and analysis of samples for a wide variety of toxins in a single run. To ensure accuracy of results, validated methods and appropriate certified reference materials (CRMs) are required. CRMs are essential for accurate instrument calibration, for assessing the complete analytical method from sample extraction to data analysis, and for verifying trueness. However, CRMs have hitherto only been available for single toxin groups.Production of a CRM containing six major toxin groups was achieved through an international collaboration. Preparation of this material, CRM-FDMT1, drew on information from earlier studies as well as improved methods for handling bulk tissues, production of reference materials, and isolation of toxins. Previous investigations of stabilisation techniques indicated freeze-drying to be a suitable procedure for preparation of shellfish toxin RMs and applicable to a wide range of toxins. CRM-FDMT1 was initially prepared as a bulk wet tissue homogenate with planned concentrations of domoic acid, okadaic acid, dinophysistoxins, azaspiracids, pectenotoxins, yessotoxin and spirolides. The homogenate was then freeze dried, milled and bottled in aliquots suitable for distribution and analysis. The moisture content and particle size distribution were measured, and determined to be appropriate. A preliminary toxin analysis of the final material showed a comprehensive toxin profile.