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.
During the downstream process of bio-based bulk chemicals, organic impurities, mostly residues from the fermentation process, must be separated to obtain a pure and ready-to-market chemical. In this ...study, capillary electrophoresis was investigated for the non-targeting downstream process monitoring of organic impurities and simultaneous quantitative detection of lactic acid during the purification process of fermentatively produced lactic acid. The downstream process incorporated 11 separation units, ranging from filtration, adsorption and ion exchange to electrodialysis and distillation, and 15 different second-generation renewable feedstocks were processed into lactic acid. The identification of organic impurities was established through spiking and the utilization of an advanced capillary electrophoresis mass spectrometry system.
A total of 53 % of the organic impurities were efficiently removed via bipolar electrodialysis; however, one impurity, pyroglutamic acid, was recalcitrant to separation. It was demonstrated that the presence of pyroglutamic acid disrupts the polymerization of lactic acid into poly lactic acid. Pyroglutamic acid was present in all lactic acid solutions, independent of the type of renewable resource or the bacterium applied. Pyroglutamic acid, also known as 5-oxoproline, is a metabolite in the glutathione cycle, which is present in all living microorganisms. pyroglutamic acid is found in many proteins, and during intracellular protein metabolism, N-terminal glutamic acid and glutamine residues can spontaneously cyclize to become pyroglutamic acid. Hence, the concentration of pyroglutamic acid in the lactic acid solution can only be limited to a certain amount.
The present study proved the capillary electrophoresis system to be an important tool for downstream process monitoring. The high product concentration encountered in biological production processes did not hinder the capillary electrophoresis from separating and detecting organic impurities, even at minor concentrations. The coupling of the capillary electrophoresis with a mass spectrometry system allowed for the straightforward identification of the remaining critical impurity, pyroglutamic acid. Although 11 separation units were applied during the downstream process, the pyroglutamic acid concentration remained at 12,900 ppm, which was comparatively high. All organic impurities found were tracked by the capillary electrophoresis, allowing for further separation optimization.
: Profiling illicit ecstasy tablets has the potential to become an invaluable tool in the crackdown on drug trafficking, but that potential has yet to be fully realized. The impurity profile of an ...ecstasy tablet can be used to determine the method employed to synthesize the actual controlled substance, which in most cases, is 3,4‐methylenedioxymethamphetamine (MDMA). Tablets can then be linked to a common synthetic route, potentially to a common manufacturer, and possibly even to a common manufacturing batch, based on the impurities present. Current methods for profiling MDMA tablets typically involve extracting the organic impurities for analysis by gas chromatography‐mass spectrometry. The potential of profiling the trace metals present in tablets has begun to be investigated while more robust statistical and chemometric procedures are being applied to compare and link tablets. This article reviews the recent advances in MDMA impurity profiling from 2002 up to the end of 2006.
Electroplating Cu technique becomes more and more important in advanced three-dimensional integrated circuit (3D-IC) packaging because of its advantages in the electrical/thermal conductivity, low ...cost, and hole-filling performance. Formula of the Cu electroplating solution, especially the additive like suppressor, accelerator, and leveler, plays a crucial role in the electroplating process. Previous studies have indicated that some organic impurities originated from the additives were incorporated in the Cu plated layer during the electroplating process. Moreover, the incorporated organic impurities segregated to the interface between the Cu plated layer and solder in a solder joint and led to formation of voids at the Cu/solder interface. In this study, effects of additive formula and plating current density on the Cu/solder interfacial reactions thermally aged at 150 and 200 °C were further investigated. If the additive formula contained only suppressor, the grain size in the Cu electroplated layer became bigger and the void quantity reduced as the current density reduced. However, when accelerator was added in the plating solution, an opposite trend was observed. The grain became smaller and a larger number of voids formed at the Cu/solder interface as the current density reduced.
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