Reference standards are standard substances used for identification, inspection, and content determination, prepared, calibrated, and supplied by units of the State Council's drug regulatory department. Standard substance refers to a standard substance used for the determination of content or potency in biological assays, antibiotics, or biochemical drugs, calibrated with a standard substance; Unless otherwise specified, reference standards should be calculated based on dryness before use. Reference substance refers to a specific substance used for the determination of physical and chemical properties of biological products, prepared by the production unit using the same method as the production process of the product. The reference substance should be as consistent as possible with the original formulation of the product. For those with poor stability, suitable stabilizers that do not contain interfering substances can be added. The reference standard shall be reviewed and recognized by the national drug inspection agency, and its standard shall not be lower than the quality standard of the product.

Reference standards refer to standard substances used for identification, inspection, content determination, and calibration of instrument performance, while standard standards refer to standard substances used for biological testing, antibiotic or biopharmaceutical content or potency determination, expressed in potency units (U). In literature, two concepts are often confused, thinking that a reference substance is a standard substance, with only one substance and two different formulations. The reason for this error may be that some drugs have both a reference substance and a standard substance. For example, when using microbiological methods to determine the potency of cefaclor, cefaclor standard is used, while when using HPLC or UV methods, the reference substance is used; When using phenacetin as a melting point calibration substance, a melting point standard is used. When determining the content, a reference substance is used. Even standard and reference materials of the same substance may have different specifications, calibration methods, and uses.

The mixed use of reference or standard substances, which refers to the use of reference or standard substances for content determination that is not the calibration method, is a common but overlooked issue in drug testing. Although there is a good correlation between the contents of different calibration methods for the same batch of reference materials, they are not the same and sometimes the differences can be significant. The reference standard for cefuroxime axetil provided by Glaxo in the UK, calibrated to 96.9% by HPLC, is used for content determination; UV is 98.9% for dissolution determination. Although the Chinese Pharmacopoeia explicitly states that the reference standards issued by the Ministry of Health are only used for the analytical methods specified in the main text. However, due to the lack of detailed instructions for the use of reference materials provided by the Ministry of Health, most of them do not have quality requirements and calibration methods for reference materials; Lack of understanding of the correct use of reference or standard materials; It is extremely difficult to find corresponding reference materials in daily scientific research; In the main text of the Chinese Pharmacopoeia, there is often a problem of mixing reference standards. As usual, the standard or reference standards used for content determination are used for dissolution testing, and the methods for content determination and dissolution analysis are different, which can easily lead to mixing.