Impurity profile identification

H. Kramer, S. Semel J.E. Abel, Trace Elemental Survey Analysis of Trinitrotoluene , PATR 4767 (1975) (An evaluation of the applicability of spark source mass spectrometry and thermal neutron activation for the detn of origin-related trace elemental impurities in TNT) 10) C. Ribando J. Haber-man, Origin-Identification of Explosives Via Their Composite Impurity Profiles I. The... 

Ref C. Ribaudo J. Haberman, Origin— Identification of Explosives Via Their Composite Impurity Profiles, I, The Relation of the Origin of Military Grade TNT to its Mono-, Di-, and Trinitrotoluene Isomer Impurities , PATR 4768 (1975)... 

The most common types of analyses are the identification test, the quantitative determination of active ingredients or major component, and the determination of impurities. The identification test provides data on the identity of the compound or compounds present in a sample. A negative result signifies that the concentration of the compound(s) in sample is below the DL of the analyte(s). The quantitative method for the major component provides data of the exact quantity of the major component (or active ingredients) in the sample, and a reported concentration of the major component must be higher than the QL. In a Determination of impurities test, one obtains data regarding the impurity profile of a sample, and can be divided into a limit test or quantitative reporting of impurities (see Table 1, which has been modified from Refs. [1] and [8]). 

Impurity testing is pivotal in pharmaceutical development for establishing drug safety and quality. In this chapter, an overview of impnrity evaluations of drug substances and products by HPLC is presented from both the laboratory and regulatory standpoints. Concepts from the development of impurity profiles to the final establishment of public specifications are described. Useful strategies in the identification and quantification of impurities and degradation products are summarized with practical examples to illustrate impurity method development. 

Various international pharmacopoeias help assure the quality of drugs worldwide. These pharmacopoeias constantly review and revise their monographs. A different impurity profile can be anticipated if a drug s production process is changed this results in the development of new analytical methods that need to be incorporated in the pharmacopoeias. In earlier editions, color reactions were performed for identification and purity evaluation purposes. 

CE is applied to two major categories of quality release testing identity and impurity testing. Identification assays are intended to ensure the unique identity of an analyte in the sample. This is normally achieved by comparison of a property of the sample (e.g., spectrum, chromatographic behavior, chemical reactivity, etc.) to that of a reference standard. As shown in Figure 9, CZE can be used to determine identity for monoclonal antibodies and proteins based on their unique electrophoretic profile. 

This study evaluated the impurity profile of untreated water from a textile plant in Portugal [35]. The organic material was concentrated by extraction from 11 of water into dichloromethane and HPLC-NMR and HPLC-MS experiments were carried out using a reverse-phase separation with an acetonitrile/ D2O gradient elution with H NMR spectroscopic observation at 600 MHz. For the HPLC-NMR studies, the samples were further fractionated into two pools according to their HPLC retention times. The HPLC-NMR studies were carried out in the stop-flow mode and the combination of NMR and MS results yielded the identification or tentative identification of 14 compounds, comprising mainly surfactants, anthraquinone dyes and nonylphenol-related molecules. 

Legal/patent protection Impurity/degradant Identification Impurity profiling Eckers et al., 1997... 

CMC information It should contain sufficient detail to assure identification, quality, purity, and strength of the investigational drug. It should include stability data of duration appropriate to the length of the proposed study. FDA concerns to be addressed focus on products made with unknown or impure components, products with chemical structures known to be of likely high toxicity, products known to be chemically unstable, and products with an impurity profile indicative of a health hazard or insufficiently defined to assess potential health hazard, or poorly characterized master or working cell bank. 

In practice, it is impossible to obtain medication of 100 % purity, which makes it necessary to check the impurity profile of the dmg. Investigations involve the isolation, identification, and quantification of the impurities, and in many cases define their biological activity and toxicity. Performing such studies is an important part of the development of a dmg and is a part of safe pharmacotherapy. The goal is to prevent tragedies, such as one in 1938 when 105 people died after administration of Elixir Sulfanilamide that was contaminated with diethyl glycol [6]. 

Trace analysis is very important in the analysis of impurities present in the active substances of dmgs and in final pharmaceutical preparations. Identification and characterization of the impurity profile of dmgs is regulated with international standards, and is used to ensure the quality of pharmaceutical products. 

Mak, M., Czira, G., Brlik, J. Mass spectrometry in impurity profiling. In Gorog, S. (ed.) Identification and Determination of Impurities in Drugs. Elsevier, Amsterdam (2000)... 

Finally, impurity analysis can also be utilized to demonstrate illegal use of patented reaction routes. The impurity profile of a drug substance is influenced by the synthetic route and the source and quality of the starting materials. Identification of impurities in drug prepared by two different manufacturers may provide valuable insight into the manufacturing route and determine if patent infringement has occurred, because certain impurities may be indicators of a specific synthetic route. 

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