Containers for reference substances should afford protection from moisture, light, and oxygen. From the point of view of the stability of the substances, sealed glass ampoules are the best containers, but they suffer from certain disadvantages, notably the risk of contaminating the substance with glass particles when the ampoules are opened and the difficulty of re-closure. Sealed ampoules are therefore principally used for materials that must be kept in an oxygen-free atmosphere. Certain materials may require even more elaborate protection. Most chemical reference substances, however, are conveniently supplied in re-closable containers, which should be uniform in type and size to facilitate distribution. It is emphasized that the permeability of containers to moisture is an important factor in determining their suitability as containers for reference substances.
The packing of a batch of a reference substance into containers is a small-scale operation for which suitable equipment is not always available to the manufacturer of the substance. Therefore the packing of reference substances is usually undertaken by the authorities responsible for them.
Vibration spatulas and similar devices are available for dispensing substances on a small scale, but these should be used with caution because of the risk of segregation of particles of different size during the filling operation, which may lead to inhomogeneity. Screw-type feeders have also been constructed, but as yet are not commercially available, and so far the packing of reference substances has been done manually.
Several pharmaceutical reference substances have to be packed under nitrogen or in conditions of controlled humidity. The use of a glove-box is of great value in this connexion.
The various stages in packing reference substances should be controlled to avoid contamination of the sample, mislabelling of containers, and other factors that might result in an unsatisfactory reference substance.
Information about suitable storage conditions for reference substances can often be obtained from the manufacturer and should be requested routinely when a new reference substance is established. Theoretically the stability of the substances should be enhanced by keeping them at low temperatures but, for substances that contain water, storage below 0 °C may impair the stability. It should also be remembered that the relative humidity in normal refrigerators or cold-rooms may be high and, unless ampoules or other tightly closed containers are used, the intended improvement in stability by storage in such places may be more than offset by degradation due to the absorption of moisture. Storage at about + 5 °C with precautions to prevent such absorption has proved satisfactory for most chemical reference substances.