4.3. Acceptance criteria

The specification of the acceptance criteria for precision is quite difficult because the criteria should be tailored to each specific application, or as it is called, methods should be “fit-for-purpose”. ICH, Eurachem and IUPAC do not specify the acceptance criteria for precision. FDA and EMA say that the within-run and between-run CV should be within 15% of the nominal value (20% at LoQ level). SANTE/SANCO and EU directive 2002/657/EC state that the CV should be smaller than 20%.

It is important to keep in mind that ideally the determination of precision should be carried out for all matrices that are within the scope of the application of the method. This general principle becomes even more important for the LC–MS methods, where the matrix influence can be significant (sample preparation, ionization suppression, etc.).

For LC–MS, it is important to determine precision at different concentrations (at least at two levels: low and high), as most guidelines suggest, since there is a strong evidence that repeatability and intermediate precision in LC-MS is concentration-dependent.