Handling different matrices in validation of analytical methods based on LC/MS

Today LC/API/MS is a method of choice in a large areas of chemical analysis where traces of organic analytes are determined in complex matrices. Another advantage is the high sensitivity and low detection levels of LC/API/MS. In API sources, especially in ESI, ionization efficiency of the analytes may be strongly altered by the compounds co-eluting (matrix compounds either from the sample analysed or very late eluting compounds from previous samples) with the analyte. The effect may either reduce (called ionization suppression) or increase (ionization enhancement) the analyte signal. This matrix effect alters not only signal but also all other validation parameters: linearity, trueness, accuracy, LoD, LoQ, robustness, etc. Also different matrices cause matrix effect with very different extent and even different sign. Therefore it is very important to adequately cover different matrices during validation. This problem of matrix effect is relevant not only for LC/MS but also for other analytical techniques from optical spectroscopy to potentiometric analyses.