2. Selectivity and identity confirmation

In this chapter we will rationalize the concepts and methods related to selectivity and confirmation of identity of analytes. No matter what kind of analysis is carried out, it is always assumed that the results express the content of analyte and not anything else.

Real-life samples are usually mixtures of many compounds mainly in matrix and consequently the analytical method must therefore be selective towards the analyte. IUPAC defines selectivity as the extent to which other substances interfere with the determination of a substance according to a given procedure [ref 52]. The larger the interference, the less selective is the procedure  (method). As the definition implies, methods can be selective to a different extent. If a given method is 100% selective, it is said to be specific. Analytical techniques are almost never generally specific or it is nearly impossible to prove that. However, analytical methods can be specific within their scope of application, i.e. for a given analyte in a given matrix in a given concentration range.

Note, that terminology regarding selectivity and specificity is not used unanimously in validation guidelines. FDA, AOAC, EMA and Eurachem guidelines use the terms suggested by IUPAC, while ICH and NordVal use the term specificity to denote selectivity.

An analytical method is regarded selective if its results are not affected by other sample components to any significant extent. Compounds, other than analyte, which contribute to the analytical signal, are called interfering compounds or interferents. Interfering compounds may:

1. Suppress/enhance the signal by altering chromatographic separation or detector response (the so-called “matrix effect”, see sections 5.3 and 5.4).
2. Behave like an analyte and yield the signal indistinguishable from an analyte’s signal. For example, in case of LC-UV analysis, an interferent would have the retention time very similar to that of an analyte and would absorb UV-radiation at the same wavelength as an analyte.

In the case of chromatographic methods it is very common to assess selectivity regarding chromatographic separation of compounds. The ability of the detector to further enhance selectivity is sometimes overlooked. But let’s start from selectivity provided by chromatography.