Detection of impurities

Fig. 24. A thin layer chromatography (TLC) image, documenting detection of impurities in a series of dye intermediate samples under near-UV illuinination. Columns 1 and 7 represent reference materials. Photographed with Polaroid Type 339 film in a CU-5 closeup camera.

The detection of impurities or surface layers (e.g., oxides) on thick specimens is a special situation. Although the X-ray production and absorption assumptions used for thin specimens apply, the X-ray spectra are complicated by the background and characteristic X rays generated in the thick specimen. Consequently, the absolute detection limits are not as good as those given above for thin specimens. However, the detection limits compare very favorably with other surface analysis techniques, and the results can be quantified easily. To date there has not been any systematic study of the detection limits for elements on surfaces however, representative studies have shown that detectable surface concentrations for carbon and... 

In pharmaceutical analysis the detection of impurities under a chromatographic peak is a major issue. An important step forward in the assessment of peak purity was the introduction of hyphenated techniques. When selecting a method to perform a purity check, one has the choice between a global method which considers a whole peak cluster (from the start to the end of the peak), and evolutionary methods, which consider a window of the peak cluster, which is... 

The optical properties of bottles are a matter of crystallinity affected by nucle-ation, depending on the content and size of light-scattering polymer solids. The purity of the raw materials and the cleanness of the reactors are prerequisites for satisfactory quality. Bottle polymer should display as little contaminations as possible. The detection of impurities is carried out by the same methods as mentioned above. Thorough filtration of the polymer is therefore mandatory. It should... 

Detection of impurities and their estimation without separation, e.g. by their effect on colligative properties, or by some kind of spectroscopy, or an electroanalytical technique such as polarography. 

Detection of impurities by separation, which almost always involves the finding of unexpected peaks in some kind of chromatogram, and which may lead to identification. 

The technique of mass spectrometry (MS) is itself of no help in the detection of impurities, but in combination with gas chromatography (the GC-MS technique) it would be the method of choice for the identification of impurities. 

An important field of application of MS is the detection of impurities and products of unwanfed side reactions, for example, producfs of oxidafive processes and solvolysis, in ILs. 

HPLC has been considered a powerful technique for the analysis of synthetic food color, for the detection of impurities in single dyes and also for the separation of a mixture of dyes (153). Re-versed-phase ion-pair chromatography has been found particularly useful for the separation and detection of a large number of food colors (159). 

General Investigation of the Impurities.—The tests described among the general methods for the detection of impurities are usually long and delicate, and when it is necessary to obtain rapidly indications as to the purity of a spirit, the following preliminary tests may be used. 

Analysis of white lead includes, besides technical tests [see General Methods), qualitative examination for the detection of impurities and adulterants [see paragraph i) and certain quantitative determinations (see succeeding paragraphs),... 

Evans, E. H. Wolff, J.-C. Eckers, C. 2001. Sulfur-specific detection of impurities in cimetidine drug substance using liquid chromatography coupled to high resolution inductively coupled plasma mass spectrometry and electrospray mass spectrometry. Anal. Chem., 73,4722-4728. 

Peptide mapping has been widely used for characterization of protein products, and is almost always used for confirmation of identity. Generally, peptide mapping is not a very sensitive technique for detection of impurities in our experience, derivatives present at levels below a few percent are not normally detected in peptide maps, whereas HPLC of the intact protein can generally detect 0.1% of such derivatives. However, in relatively simple maps such as the V-8 protease digest of insulin, relatively good limits of detection can be achieved (5). 

In the method validation, low concentrations of the product are used for the detection of the target protein, while high concentrations are recommended for the detection of impurities. 

The standard tools such as FTIR, NMR, MS and UV-Vis are not sufficient for the requirements of nonaqueous electrochemistry, that is, detection of impurities in the solvents at a ppm level. The best of these methods, the NMR, can detect impurities only at a subpromil level, which is too high. As discussed in the chapter dealing with the electrochemical windows of nonaqueous systems, a few tens of ppm of contaminants can considerably affect the electrochemical behavior. Therefore, GC or HPLC are the only appropriate methods available today [3-5], However, it is important to note that there are solvents that can partially decompose in the injection port or in the column of the GC. The relevant solvents are those whose normal boiling points are high, and thus their GC analysis requires high temperatures. For example, PC, EC, BL and SL are typically problematic for GC analysis. 

The refractive index of a transparent substance is the ratio of the velocity of light in air to its velocity in that material under like conditions. It is equal to the ratio of the sine of the angle of incidence made by a ray in air to the sine of the angle of refraction made by the ray in the material being tested. The refractive index values specified in this Codex are for the D line of sodium (589 nm) unless otherwise specified. The determination should be made at the temperature specified in the individual monograph, or at 25° if no temperature is specified. This physical constant is used as a means for identification of, and detection of impurities in, volatile oils and other liquid substances. The Abbe refractometer, or other refractometers of equal or greater accuracy, may be employed at the discretion of the operator. 

The use of NMR and IR spectroscopy has been recommended for the identification of phenothiazine drugs and detection of impurities in samples of such drugs, inasmuch as the substituents, and particularly the side chain, give rise to characteristic groups of signals. 

Direct quantification is carried out in situ rather than after spot elution. The simplest direct method involves visual comparison of sample zone size and/or intensity (color) variation according to concentration against reference standards developed on the same plate.f This qualitative/semiquantitative approach is specified in various pharmacopeias for the purity analysis of active raw materials and formulated products. These pharmacopeial methods are designed for analyses at several levels 1) simple detection of impurities as additional spots 2) detection and identification of impurities by comparison to the R( values distances of standards or 3) detection, identification, and estimation of amounts of impurities by comparing intensities between samples and standard dilutions of the same compounds. ... 

The author s work on the HPLC analysis of taxines was a follow-up of previous research work on the HPLC of taxanes. Unknown peaks present in the analysis of plant and cell culture extracts were suspected to be taxines. In previous works, several other researchers have reported the detection of impurity peaks in the extracts of Taxus X media (Hicksii) needles during the determination of taxanes. These uncharacterized impurities showed a UV maximum at 280 nm, with a A280/A228 ratio of approximately 3.5. Using absorbance ratio with these two or similar wavelengths, the researchers managed to overcome quantitation problems.Taxines and taxinines were also reported to cause problems in the HPLC analysis of taxanes, coeluting with the peak of paclitaxel. 

FdPLC has contributed many successes in product development and in quality control for the pharmaceutical industry. The UV detector coupling with HPLC equipment is the most important analytical instrument for preformulation, QC/QA, and in-process control in pharmaceutical analysis. HPLC is a basic and reliable analytical tool for preformulation study because of the high-resolution capacity, accuracy, and reproducibility of the equipment. Its primary function includes search for and detection of impurities in drug substances, as well as stability evaluation of dosage forms in terms of detection and quantitation of degradation products. 

The essential aspects have been discussed in the introduction on the use of RMs and CRMs. It should be noted that inorganic CRMs, in particular pure metals, are available on the market from several reliable suppliers. They show usually purity values with associated uncertainties that are negligible compared to the uncertainty of the majority of spectrometric methods in which they serve as calibrants. It is usual to find materials of stated (not by definition certified) purity of 99.999% (five nines in analytical jargon) or better. This would mean that any impurity is below 0.001% as a mass fraction. No relative analytical method has precision performances that go down to such levels. Suppliers of ultra pure metals are numerous. NIST sells such metals as certified RMs (SRMs). The certification of the purity is discussed briefly in Chapter 5. It can be mentioned that the measurements are often based on absolute methods. The ultimate detection of impurities can be made with spark source MS. For pure metals the uncertainty linked to the calculated purity is small. Therefore, compared to the intended use and the uncertainty of classical methods applied by the analyst for the determination of elements, it is totally negligible. 

The development of new separation methods for the analysis of drugs is continuously requested during drug design, development, production, and use. In this regard, some analytical issues are of particular importance, including purity assessment, analysis of isomers, detection of impurities, and/or related compounds. Although most of the methods used for pharmaceutical analysis involve... 

Analytically, PEG reagents have very few properties that can be exploited to enable separation and detection of impurities and degradants. As discussed in the chemistry section, PEG reagents are... 

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