Retrospective analysis of the stability of reference substances developedby the Reference Substances Service of the National Institute of Medicines

Abstract

The development of a Reference Substance (RS) is an elaborate procedure in which a series of stages must be rigorously carried out on a homogeneous material of adequate purity. The storage conditions chosen for the source material must be studied and established to maintain its quality and integrity over time, avoiding any possible degradation. The quality of the RS impacts on the quality assurance of the raw material or medicinal specialty which contains it, therefore, it is important to consider that, if any deterioration is found in the RS, the results obtained may affect compliance with the specified technical requirements. The main purpose of this research work was to prove retrospectively the importance of monitoring and evaluating the purity profile in order not to assign an arbitrary expiration date, avoiding the discarding of undamaged material. For this purpose, various attributes (percentage of impurities, water content or humidity percentage, assay, and crystalline purity) of different RS made by the Reference Substances Service of the National Institute of Medicines were evaluated. As a result, a very low variability was observed in the diverse attributes evaluated, which could indicate that these substances preserve their characteristics over time and that a periodic re-assessment could be a suitable strategy in order to prevent unnecessary discarding.