**9. Aspects of analytical quality**

LC-MS/MS is currently considered as the method of choice for quantitative analysis of drugs and their metabolites. The advantages of using this technique in MRM mode due to high sensitivity, selectivity and speed allow developing high throughput methods with little or no sample preparation and minimal chromatographic retention. However, matrix effect may have a significant impact on such LC-MS/MS analyses [94, 102, 103]. Therefore, the evaluation of matrix effect as well as strategies for its elimination or minimization needs to be adequately addressed. Another important parameter for analytical quality is the selection of an appropriate internal standard for the compensation of possible loss of analytes during sample clean up and variations in instrument performance. Other LC-MS/MS issues, such as ion channel cross-talk and carry-over should also not be overlooked. Moreover, metabolite instability may have an influence on the analytical performance and will be additionally addressed here.
