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1.8 REFERENCE SUBSTANCE

        A Reference Substance is an authenticated uniform material that is intended for use in specified chemical, physical and biological tests, by which the properties of the product under examination are compared.  Reference Substances are needed for certain analytical procedures in many monographs of the Thai Pharmacopoeia including:
        (1) infrared identification;
        (2) spectrophotometric or photometric methods of assay;
        (3) chromatographic tests and assays;
        (4) biological tests and assays including microbiological assays; and
        (5) others.
      Where a test or an assay calls for the use of a Reference Substance, the Department of Medical Sciences Reference Substances (DMScRS), ASEAN Reference Substances (ARS) or other recognized reference substances may be used. The DMScRS and ARS are available from Bureau of Drug and Narcotic, Department of Medical Sciences (DMSc), Nonthaburi, Thailand. 

DMSc Reference Substance and ASEAN Reference Substance

      The ARS project was established in 1980 under the Technical Cooperation among ASEAN countries on Pharmaceuticals in order to produce reference substances for utilization within ASEAN region. The project was supported by United Nations Development Program (UNDP) and World Health Organization (WHO) from 1982 to 1991 and Japan Pharmaceutical Manufacturers Association (JPMA) from 1992 to 2018. The DMScRS and ARS are recognized as secondary reference standards according to the definition of WHO Technical Report Series No. 943, 2007.

       The DMScRS was initiated in 1993 following the requirements stated in the International Standard ISO 17034. To date, 67 DMScRS have been produced and distributed for utilization in pharmaceutical quality control laboratories. A model of the testing protocol is set up by the DMSc. The testing protocol may comprise identification tests (e.g., infrared absorption, UV-absorption), determination of physico-chemical constant (e.g., melting range, specific rotation, specific gravity), chromatographic purity test, inorganic contaminants determination, volatile substances test (e.g., water, solvents), functional group analysis (e.g., titrations, UV absorptivity), thermal analysis (e.g., differential scanning calorimetry), and assay against another well-characterized standard (e.g., USPRS, BPCRS and EPCRS).

Label Text

        The label text is designed to provide the user with the information needed for the correct storage and usage of the reference substances in monograph application(s). The label includes an assigned value for purity of reference substances with quantitative applications as well as storage conditions. DMScRS and ARS are accompanied by certificate of analysis with more details of testing results, intended use, direction for use, and storage conditions.

Packaging and Storage

         DMScRS and ARS are packaged in individual units designed to maintain the integrity of reference substances. The most common containers for solid material are colourless or amber glass vial with plastic inner and screw cap. The packaging environment is determined by the sensitivity of the material to light, oxidation, or atmospheric humidity. Where appropriate, containers are filled in a glove box under inert gas and in conditions of controlled low residual humidity. To serve its intended purpose, the DMScRS and ARS must be properly stored, handled and used. Generally, reference substances should be stored in their original containers away from heat and protected from light. Avoid humid storage areas in particular.

Continued Suitability for Use Program

         To ensure that the reference substances maintain the properties determined at the initial evaluation, the DMSc maintains a continued suitability for use program. The retesting intervals and protocols are a function of the uses and properties of the substance and of the information available about its stability. Abbreviated protocols use the stability-indicating methodology employed in the initial characterization of the material to confirm the consistency of attributes such as appearance, chromatographic purity, or volatiles content.

Proper Use

          The reference substances are not intended foruse as drugs. DMScRS and ARS do not carry an expiration date, but a retest date, as long as they are in distribution. An updated version of catalogue can be found on the BDN website at https://bdn.go.th. Whenever the directions for use specified in the certificate of analysis require a preliminary drying or a correction for volatiles, it should be performed “at the time” of use. Further experimental details should be controlled by the user’s Standard Operating Procedures and Good Laboratory Practices.