Impurity is not a much-liked word by pharmaceutical and industry people, because they are concerned about quality. Here we discuss various impurities that might be present in API formulations. To fulfill our purpose we have compiled a variety of regulatory authorities’ guidelines (i.e., ICH, WHO, and pharmacopoeias), which serve in endlessly regulating the impurities by various means. As the impurity present in a drug can affect its quality and thus its efficiency, it is therefore crucial to know about impurities. The current article reveals the different terms, regulatory control, and basic techniques (e.g., HPLC, LC-MS, TLC) that will help novices to understand, identify, and quantitatively estimate impurities and that have the advantage of profiling. This article primarily focuses on identification and control of various impurities (i.e., organic, inorganic, and genotoxic). For any of the substances, quality is the prime objective. Because impurities can alter quality, understanding the various impurities will help in producing quality products.
The pharmaceutical world is dedicated to quality. Speaking from the customer’s perspective, quality means pleasant appearance with good packaging. But in the case of pharmaceutical industries, quality means providing drug standards conforming to a variety of conditions and making profit from them. So, they should be aware of the various types of impurities and their regulation and control, which infer quality. Therefore, in this paper we have tried to summarize different types of impurities, along with their effects and limitations as given by the International Conference on Harmonization (ICH). ICH has given guidelines [ICH Q-3B (R2) 2006] for impurity in a drug, and according to ICH, it is a chemical entity, which is not defined as a drug per the Drugs and Cosmetic act and which has an impact on the purity of the active pharmaceutical ingredient or drug substance.
Every pharmaceutical manufacturer defines impurity in its own words, making it difficult to find an exact definition of impurity. In the pharma world, impurity can be identified by various terms that we will see later. Drug substances or drug products are prepared with various solvents. Remaining solvents or residual solvents that might be present in the final product often are cited as organic volatile impurities (OVI) (ICH Q-3C [R4] 2009), and the impurities associated with the inactive pharmaceutical ingredients used in formulation or as additives or adjuvants are rarely mentioned.
Bulk pharmaceutical chemicals (BPCs), can be obtained or synthesized from multiple sources and, therefore, it is very important that impurities in BCPs be carefully monitored and controlled. Recently British pharmacopoeia (BP), United State Pharmacopoeia (USP), and Indian pharmacopoeia (IP) started incorporating allowable limits of impurities present in drug substances or drug products (Kovaleski et al. 2007, Gad 2008). This article thoroughly reviews different impurities found in the pharmaceuticals by methods for isolation, extraction, and identity of possible impurities.
Impurity should be defined as identified impurity– an impurity available with information about the structural characterization, and unidentified impurity– an impurity that can be identified only with qualitative analytical values (e.g., peak area, retention time, etc.), for which structural information is not yet available.
Impurities present in new drug substances used in clinical and safety trials are covered under two aspects [ICH Q-3A (R2) 2006]. Chemistry aspects classify and identify impurities, generate the report for different impurities, list various impurities present in any substances, and give a brief discussion of analytical procedures for impurity detection. Safety aspects include those impurities that are present at a considerably lower amount or not present at all in a discovery of new drug substance.
A number of terms have been commonly used to describe an impurity or impurities (Francis et al. 1984, McNaught and Wilkinson 1997):