Pharmacopeia impurities

Bulk production of United States Pharmacopeia (USP) and reagent grades is based on the reaction of sodium carbonate or hydroxide with an acidic iodide solution, typically hydriodic acid or a metal iodide. After removal of chemical impurities, the solution is filtered and concentrated. Evaporation gives the anhydrous Nal. Controlled cool-down produces either the dihydrate or the pentahydrate [81626-33-7]. 

Impurities that cause the greatest concern are those that are toxic, defined by the US Pharmacopeia (USP) as impurities that have significant undesirable biological activity [ 1 ], and host cell contaminants in biopharmaceuticals that have potential risks of allergic reaction or other immunopathological effects [2]. 

Sulfuric acid comes in different grades technical, which is colored and contains impurities but which can be used to make fertilizer, steel, and bulk chemicals certified pure (CP) and U.S. Pharmacopeia (USP). The last two are used to make batteries, rayon, dyes, and drugs. Rubber or lead-lined containers can be used for dilute acid iron, steel, or glass can be used for concentrated acid. Shipments require a white DOT label. 

The ICH also provides guidelines in analytical validation [Q2(R1), impurities (Q3 series), pharmacopeias (Q4 series), quality of biotechnological products (Q5... 

The subject of impurity analysis of pharmaceutical compounds has been insufficiently addressed in the scientific literature. Many monographs in die U.S. Pharmacopeia have nonspecific assay methods. An attempt has been made to address this problem by focusing on specific methodologies and delineating origination and concentration of impurities found in pharmaceutical compounds. 

The United States Pharmacopeia (USP) test (467) describes three different approaches to measuring organic volatile impurities in pharmaceuticals. Method I uses a wide-bore coated open tubular column (G-27, 5% phenyl-95 % methylpolysiloxane) with a silica guard column deactivated with phe-nylmethyl siloxane and a flame-ionization detector. The samples are dissolved in water and about 1 p is injected. Limits are set for benzene, chloroform, 1,4-dioxane, methylene chloride, and trichloroethylene. Methods V and VI are nearly identical to method I except for varying the chromatographic conditions. For the measurement of methylene chloride in coated tablets, the headspace techniques described above are recommended. 

The determination or investigation of inorganic components is relatively seldom carried out in pharmaceutical chemistry. It occurs, for example, in the determination of heavy-metal impurities in chemicals or pharmaceuticals, originally by d.c. polarographic methods, but anodic stripping analysis as described at the beginning of this chapter would be more convenient, or the determination of zinc present in zinc-protamine-insulin as prescribed by the Czechoslovak pharmacopeia [197]. 

Direct quantification is carried out in situ rather than after spot elution. The simplest direct method involves visual comparison of sample zone size and/or intensity (color) variation according to concentration against reference standards developed on the same plate.f This qualitative/semiquantitative approach is specified in various pharmacopeias for the purity analysis of active raw materials and formulated products. These pharmacopeial methods are designed for analyses at several levels 1) simple detection of impurities as additional spots 2) detection and identification of impurities by comparison to the R( values distances of standards or 3) detection, identification, and estimation of amounts of impurities by comparing intensities between samples and standard dilutions of the same compounds. ... 

At the first biennial meeting of the ICH in Brussels in November 1991, the United States, Japanese, and European Pharmacopeias presented papers relating to progress being made in the harmonization of pharmacopeial standards for excipients. Other topics, such as stability, validation, impurities, and biotechnology, were established. The pharmacopeias are involved in all these issues. In fact, USP general chapters served as background for harmonization for some of these topics. ° ... 

For some years, the USP had a requirement on organic volatile impurities. When the EP was adopting a similar requirement, it was clear that toxicologists on different sides of the ocean would come to different conclusions as to appropriate limits on solvents. At the request of the pharmacopeias, this topic was taken... 

The ICH guideline on impurities is also integrated into the technical guide, and the guideline on residual solvents has been integrated into a general chapter of the European Pharmacopeia. 

This guide is intended for the experts who participate in the elaboration of European Pharmacopeia monographs it establishes the general rules to be followed. This document specifies the philosophy behind the choice of techniques for identification testing of a substance and for the determination of the limit contents of impurities and the methods used to detect them. 

The United States Pharmacopeia (USP)8 discusses impurities in various... 

The pharmacopeia states that our notions about purity are likely to change with time and that purity is closely related to current developments in analytical chemistry. Therefore, what we regard as pure today may be considered impure at some future time if methods are found that can determine other components in a particular compound. Inorganic, organic, biochemical, isomeric, or polymeric components may all be considered impurities. The following terms have been used to describe impurities ... 

A number of requirements have an effect on monitoring impurities (see Chapter 2). For example, a country s pharmacopeia or the one accepted by that country often provides the primary guidance as to how impurities are to be monitored and regulated. In a majority of countries these pharmacopeias are run under the auspices of the government. The USP is a notable exception to this case. If a product is considered a pharmacopeial item, it must meet the compendial requirements. 

In addition to the above, the United States Pharmacopeia (USP) addresses impurities using additional terminology 4 foreign substances and other impurities, toxic impurities, and ordinary impurities. 

Table 5.5. Limits of radionuclidic impurities in the eluate of fission Pharmacopeia)...

Shukla SK, Manni GB, Cipriani C (1977) Effect of aluminium impurities in the generator-produced pertechnetate-99m ion on thyroid scintigrams. Eur J Nucl Med 2 137-141 United States Pharmacopeial Convention (2005) Official monographs USP 28, sodium pertechnetate Tc injection. United States pharmacopeia (USP) 28 - national formulary (NF) 23, p 1861... 

Radiochemical Purity. The European Pharmacopeia requires thin-layer chromatography (TLC) (distance 10-15 cm) for the identification of impurities using methylethylke-tone (MEK) as solvent. The radioactivity corresponding to Tc-HSA must not be less than 95% (Council of Europe 2005). 

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