RELATED SUBSTANCES (@PharmaScholars )

U.S. PHARMACOPEIA Search USP29 1086 IMPURITIES IN OFFICIAL ARTICLES Concepts about purity change with time and are inseparable from developments in analytical chemistry. If a material previously considered to be pure can be resolved into more than one component, that material can be redefined into new terms of purity and impurity. Inorganic, organic, biochemical, isomeric, or polymeric components can all be considered impurities. Microbiological species or strains are sometimes described in similar terms of resolving into more than one component. Communications about compendial articles may be improved by including in this Pharmacopeia the definitions of terms and the contexts in which these terms are used. (See Definitions below.) There has been much activity and discussion in recent years about term definition. Certain industry-wide concerns about terminology and context deserve widespread publication and ready retrievability and are included here. (See Industrial Concepts below.) See Foreign Substances and Impurities, in the section Tests and Assays, under General Notices and Requirements, as well as the recently adopted general chapter, Ordinary Impurities 466. Some other general chapters added over the years have also addressed topics of purity or impurity as these have come into focus or as analytical methodology has become available. Analytical aspects are enlarged upon in the chapter Validation of Compendial Methods 1225. Monographs on bulk pharmaceutical chemicals usually cite one of three types of purity tests: (1) a chromatographic purity test coupled with a nonspecific assay; (2) a chromatographic purity-indicating method that serves as the assay; or (3) a specific test and limit for a known impurity, an approach that usually requires a reference standard for that impurity. Modern separation methods clearly play a dominant role in scientific research today because these methods simultaneously separate and measure components and fulfill the analytical ideal of making measurements only on purified specimens. Nevertheless, the more classical methods based on titrimetry, colorimetry, spectrophotometry, single or multiple partitions, or changes in physical constants (or any other tests or assays) lose none of their previous validities. The purity profile of a specimen that is constructed from the results of experiments using a number of analytical methods is the ultimate goal. DEFINITIONS Foreign Substances Foreign substances, which are introduced by contamination or adulteration, are not consequences of the synthesis or preparation of compendial articles and thus cannot be anticipated when monograph tests and assays are selected. The presence of objectionable foreign substances not revealed by monograph tests and assays constitutes a variance from the official standard. Examples of foreign substances include ephedrine in Ipecac or a pesticide in an oral liquid analgesic. Allowance is made in this Pharmacopeia for the detection of foreign substances by unofficial methods. (See Foreign Substances and Impurities, in the section Tests and Assays, under General Notices and Requirements.) Residual Solvents Residual solvents are defined as organic volatile chemicals that are used or produced in the manufacture of drug substances or excipients, or in the preparation of drug products. The solvents are not completely removed by practical manufacturing techniques. Appropriate selection of the solvent for the synthesis of a drug substance may enhance the yield or determine characteristics such as crystal form, purity, and solubility and, as such, may be a critical parameter in the synthetic process. Because there is no therapeutic benefit from residual solvents, they should be removed to the extent possible to meet product specifications, good manufacturing practices, or other quality-based requirements. Drug products should contain no higher levels of residual solvents than can be supported by safety data. A classification of residual solvents by risk assessment is presented in the Residual Solvents Limits section of Organic Volatile Impurities 467. . Related Substances Related substances are structurally related to a drug substance. These substances may be identified or unidentified degradation products or impurities arising from a manufacturing process or during storage of a material. Process Contaminants Process contaminants are identified or unidentified substances (excluding related substances and water), including reagents, inorganics (e.g., heavy metals, chloride, or sulfate), raw materials, and solvents. These substances may be introduced during manufacturing or handling procedures. (@PharmaScholars ) #Related_substances #Impurities #Organic_impurities #Inorganic_Impurities #Residual_solvents