Impurities, organic quantification

The concurrent identification and quantification of organic impurities is a principal use of liquid chromatography in the pharmaceutical industry. However, the application of liquid chromatography to this task highlights a weakness of this technique when compared to gas chromatography specifically, the lack of a universal detector. Great strides have been made to create detectors and hyphenated techniques to address these problems. However, multiple detectors and analytical procedures may be necessary to accurately and specifically identify and quantify the impurities in complex systems. 

The net result of such regulation is that there are well-developed standards for the way in which quantitative and, increasingly, qualitative measurements are carried out. There are also well-defined limits for various categories of impurity, all of which tends to emphasise the importance of measurements on the final API rather than on the process that produces it, for which the requirement is simply that the process remains under control . The importance of this summary is that at present, whatever the means of production, there is a requirement that the API will reach certain standards of purity as demonstrated by end-point measurement. Those standards effectively demand quantification of impurities down to about 0.05% for related organic impurities, in the region of ppb to low ppm for known toxins and low ppm levels for inorganics such as catal3Tic metals. 

Gas chromatography is an extremely useful technique for quantification. It can afford the desired resolution, selectivity, and ease of quantification. The chief limitation, however, is that the sample must be volatile or must be made volatile by derivatization. This technique is very practical for organic volatile impurities (OVI). 

Simple organic acids often possess chromophores, which makes direct UV detection possible, even at low wavelengths. CE can measure the presence of small ion contaminant impurities in drug substances. For example, an NACE method with indirect UV detection was used to monitor ammonium ion contaminant in pharmaceutical preparations with a limit of detection of 50 ppb [254]. A number of reviews have been published that will provide the reader with a comprehensive coverage of the status of CE for the analysis of ions and small molecules, including detection methods, quantification, and stoichiometric determinations [8,9,11,253,255,256]. Table 4.7 shows some recent analysis applications of CE for ion analysis. 

Many amperometric sensors developed for heavy metal quantification are based on carbon nanostructured stufaces, mainly consisting of CNTs and graphene. The interaction of these nanosized materials with the analytes involves carboxyl groups localised in correspondence to the defects of the nanostmcture. However, the possible involvement of metal impurities normally present in CNTs, as well as the capability of sp hybridised carbon sites to adsorb species from the solution, should be also taken into account. On the other hand, the adsorption of many organic and inorganic species present in the solution constitutes the main drawback that limits the actual applications of carbon-based electrode materials in real matrices. Some strategies have been proposed to reduce this effect, e.g. the... 

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