Impurity analysis

Wilson, R.G., Stevie, F.A., and Magee, C.W., Secondary Ion Mass Spectrometry A Practical Handbook for Depth Profiling and Bulk Impurity Analysis, Wiley, Chichester, U.K., 1989. 

The conventional method for quantitative analysis of galHum in aqueous media is atomic absorption spectroscopy (qv). High purity metallic galHum is characteri2ed by trace impurity analysis using spark source (15) or glow discharge mass spectrometry (qv) (16). 

The subject of impurity analysis of pharmaceutical compounds has been insufficiently addressed in the scientific Hterature (3,4). Many monographs... 

The term direct TXRF refers to surface impurity analysis with no surface preparation, as described above, achieving detection Umits of 10 °—10 cm for heavy-metal atoms on the silicon surface. The increasit complexity of integrated circuits fabricated from silicon wafers will demand even greater surfrce purity in the future, with accordingly better detection limits in analytical techniques. Detection limits of less than 10 cm can be achieved, for example, for Fe, using a preconcentration technique known as Vapor Phase Decomposition (VPD). 

NAA is well suited for Si semiconductor impurities analysis. The sensitivity and the bulk mode of analysis make this an important tool for controlling trace impurities during crystal growth or fer monitoring cleanliness of various processing operations for device manufacturing. It is expected that research reactors will ser e as the central analytical facilities for NAA in the industry. Since reactors are already set up to handle radioactive materials and waste, this makes an attractive choice over installing individual facilities in industries. 

The results are qualitatively evaluated by making overlay plots. An example of an HPLC gradient separation for a typical assay and impurities analysis is shown in Figure 13a. The selectivity is evaluated on five different lots of the selected stationary phase. As can be observed, apart from two minor selectivity issues (indicated by the arrows in Figure 13a), the reproducibility on different lots of stationary phases is acceptable. 

After a short introduction into the relevance of Impurity profiling for regulatory authorities, public health, and the pharmaceutical industry, an overview is presented based on the various modes of capillary electrophoresis that have been used in drug impurity analysis. The applications of capillary zone electrophoresis, non-aqueous capillary electrophoresis, micellar electrokinetic capillary chromatography, microemulsion electrokinetic capillary chromatography, capillary gel electrophoresis, and capillary electrochromatography are presented consecutively. 

The concept of impurity profiling is very important for antibiotics, since most of them are still produced by fermentation or by semisynthesis starting from fermentation products. Antibiotics are typically complex mixtures of several components and their composition depends on the fermentation conditions. Impurities due to degradation occur frequently. Commercial samples usually contain significant amounts of impurities with only minor structural differences among them, but differing widely in their pharmacological activities. These impurities can exhibit antibiotic activity, but in many cases they are inactive and sometimes even toxic. The applicability of CE in the analysis of antibiotics has been reviewed elsewhere. The use of CZE in impurity analysis of antibiotics is discussed in detail below. 

Erythromycin, a macrolide antibiotic, lacks a significant chromophore. Detection sensitivity was enhanced by using a wavelength of 200 nm and selecting an injection solvent of lower conductivity than the BGE. In order to facilitate the separation of erythromycin and its related substances, 35% (v/v) ethanol was incorporated into a 150 mM phosphate buffer pH 7.5. Resolution of all of the compounds was achieved in approximately 45 min. The method was employed as an assay method for erythromycin and for impurity determination. Peptide antibiotics, such as colistin and polymyxin, are mixtures of many closely related compounds. A validated CZE method for impurity analysis of polymyxin B was described, employing 130 mM triethanolamine-phosphate buffer at pH 2.5 to reduce the adsorption of analyte onto the capillary wall. Methyl-/l-cyclodextrin (M-/1-CD) and 2-propanol were found to be necessary for selectivity enhancement. Using similar buffer additives, the same group developed and validated a method for colistin analysis. ... 

Most samples may be prepared by dissolution in water. The final concentration should be optimized according to the aim of the analysis, counterion or impurity analysis. For the control of impurities, the main counterion may be fairly overloaded. This may have an impact on the ionic strength of the sample and will produce a disturbed peak profile for the main compound. When solubility problems are encountered, up to 30% of methanol, ethanol, or acetonitrile may be added to improve solubility. However, the presence of too much organic solvent may produce an instrumental error, because the conductivity of the sample plug will differ too much from BGE conductivity, leading to current leakage. Or, when the sample is insoluble in water, it may be suspended, vortexed, and then centrifuged. The analysis is then performed on the supernatant as the ions are water soluble. 

Context - a brief history of drug impurity analysis... 

We have discussed one driver for drug impurity analysis, namely the need for the synthetic organic chemist to monitor his reactions. We will return to this theme later in the chapter. However, there are two other drivers for drug impurity analysis that are relevant to any discussion of change. 

An efficient analytical procedure for the trace impurity analysis of Mg, K, Cr, Mn, Fe, Ni, Co, Cu, Zn, Ag, Cd, Ba and Pb in high purity silicon powder after a very simple matrix separation via microwave assisted volatihzation of silicon as silicon fluorides, was proposed by Ueng el al.59 The authors observed a nearly 99 % volatihzation of the matrix element silicon from the... 

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. 

Alsante KM, Friedmann RC, Hatajik TD, Lohr LL, Sharp TR, Snyder KD, Szczesny EJ. Degradation and impurity analysis for pharmaceutical drug candidates. In Ahuja S, Scypinski S, eds. Handbook of Modern Pharmaceutical Analysis. Vol. 3. Separation Science and Technology. Academic Press, 2001 85-172. 

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