API- Impurity's and Reference standards.
Impurity Reference standards used in the analytical procedures for control of impurities should be evaluated and characterised according to their intended uses. Impurity standards are used for purity tests and during method development and validation of those tests. Identity must be ensured, and purity and assay must be defined.
Information on what constitutes an impurity reference standard (IRS) is scarce. The European Pharmacopoeia states. that “reference standards are established using suitable procedures and their continued suitability for use is monitored” and further “a CRS (Chemical Reference Substance) corresponding to an impurity is characterized for identity and purity.” Meanwhile the ICH simply requires in impurity guidelines Q3A/Q3B that “reference standards used in the analytical procedures for control of impurities should be evaluated and characterized according to their intended uses.” There is not much further information available, so it is not surprising that approaches to impurity standards are highly variable, from both manufacturers of such standards and end users.
A real impurity reference standard should provide identity evidence, i.e. spectra and information on how they were used for proving identity, at least comprising a short formal sentence that on request can be elaborated into a full identity interpretation report.