{Reference Type}: Journal Article {Title}: Validation challenges in liquid chromatography-tandem mass spectrometry methods for the analysis of naturally occurring compounds in foodstuffs. {Author}: Golubović J;Heath E;Heath D; {Journal}: Food Chem {Volume}: 294 {Issue}: 0 {Year}: Oct 2019 1 {Factor}: 9.231 {DOI}: 10.1016/j.foodchem.2019.04.069 {Abstract}: LC-MS/MS is the mainstream technique for the analysis of naturally occurring compounds in food. Because of the complex chemical composition of food, the most challenging validation parameters are those related to the matrix - linearity (calibration) and trueness. The influence of the interfering compounds on the analytical results is reflected in the extraction efficiency and matrix effect. These effects must be compensated for, if they cannot be removed or reduced by optimizing the extraction and the LC-MS/MS method. The calibration strategy is selected on the basis of the analytical conditions - complexity of matrix, and chemical structure and number of analytes. It is advisable to estimate trueness - both extraction efficacy and matrix effect during the preliminary experiments in order to select the right type of calibration. Finally, it is essential to describe the validation procedure in detail and refer to the used guidelines in order to provide a reproducible method.