(1999; 168 pages) [Spanish]
2. Obtaining source material
Source material of satisfactory quality can be selected from a batch (lot) of the substance originating from the normal production process, if the purity is acceptable. Further purification techniques may be needed to render the material acceptable for use as a chemical reference substance.
The purity requirements for a chemical reference substance depend upon its intended use. A chemical reference substance proposed for an identification test does not require meticulous purification, since the presence of a small percentage of impurities in the substance often has no noticeable effect on the test.
On the other hand, chemical reference substances that are to be used in assays should possess a high degree of purity. As a guiding principle, a purity of 99.5% or higher is desirable, calculated on the basis of the material in its anhydrous form or free of volatile substances. However, where the selectivity of the analytical procedure for which the chemical reference substance is required is low, such a degree of purity may not be necessary. In making a decision about the suitability of a chemical reference substance, the most important consideration is the influence of the impurity on the attribute measured in the assay when used in a non-specific assay procedure. Impurities with physicochemical characteristics similar to those of the main component will not impair the usefulness of a chemical reference substance, whereas even traces of impurities with significantly different properties may render a substance unsuitable as a chemical reference substance.
When source material to be used as a chemical reference substance is obtained from a supplier, the following should be supplied with the material:
• Certificate of analysis with complete information as to test methods employed, values found and number of replicates used, where applicable, and relevant spectra and/or chromatograms.
• Information on optimal storage conditions required for stability (temperature and humidity considerations).
• Results of any hygroscopicity study and/or statement of the hygroscopicity of the source material.
• Results of any accelerated stability studies.
• Identification of detected impurities (by preference), and/or specific information on the relative response factor as determined in compendial methods concerning the principal component, and/or the percentage mass of the impurity.
• Updated Material Safety Data Sheet outlining any health hazards associated with the material.
For new drug substances, manufacturers should be aware that elaboration of pharmacopoeial monographs will be needed and a batch of the new substance should be set aside to be used if necessary as the chemical reference substance. It is desirable for bodies that issue chemical reference substances to provide each other with a sample of the same batch of material, even if the substance will be employed for different test methods. This will require the exchange of information concerning the establishment process, supplier(s), availability and conditions of supply.