Here we describe the validation of a quantitative multi-mycotoxin method in wheat flour, which was further extended to a range of different cereal-based flours. The Waters™ Xevo TQ-XS Tandem Quadrupole Mass Spectrometer was chosen because it provides ultimate sensitivity and it allows the analyst to implement a simple sample preparation process, thus reducing the overall analysis time. The use of isotopically labelled internal standards was investigated to achieve better performance compared to the widely adopted external standard or standard addition methods. The analytical procedure was assessed according to criteria described by the amended European Commission Regulation No. 401/2006 and SANTE guidelines.