Impurities, structurally-related

Raman spectroscopy is primarily a structural characterization tool. The spectrum is more sensitive to the lengths, streng ths, and arrangement of bonds in a material than it is to the chemical composition. The Raman spectmm of crystals likewise responds more to details of defects and disorder than to trace impurities and related chemical imperfections. 

These chromatographic performance tests are carried out in order to ensure that all impurities to be controlled are well separated from the substance to be examined (HPLC, GC andTLC). Forthis reason, preferably such reference substances are chosen which elute dose to the main compoxmd (HPLC, GC) or which have a similar Rf-value (TLC) but can stiU be separated. These may be structurally related compoimds which shall be separated with a minimum requirement for the resolution using the chromatographic system described, e.g. such as in the monograph for desmopressin (Monograph 07121999), Figure 5.3. 

The following applications highlight the vastly different ways achiral-chiral LC-LC can be used. Many of these applications involve analytes that are structurally related. These structurally related compounds may be impurities from the synthesis of the analyte of interest using either traditional laboratory or biological methods. Achiral-chiral separations can be useful in separating these related analytes. 

These non-existent allotropes, which are impurity-stabilized phases, are fee Sc, fee Y-Ce, the bcc Ho, Er, Tm and Lu and fee phases of Nd, Sm, Gd and Dy, some of which have been described as formed at room temperature during mechanical milling. A number of fee high-pressure polymorphs, for instance, are actually compounds, with a structure related to the NaCl-type, formed by reaction with O, N and/or H during mechanical milling (see also Alonso et al. 1992). 

During the synthesis of food dyes, as with any chemical reaction, the product that is formed contains impurities, since the reactants themselves are usually impure and side reactions can also occur. The impurities can be of three types Uncombined intermediates are compounds from which a color is directly synthesized and do not impart color to the product subsidiary colors are colored compounds that are structurally related to the product other impurities include substances that may arise from contamination of the intermediates or other reagents used during synthesis... 

Quantification, then, requires only a single nitrogen-containing standard, which need not be structurally related to the analyte. Thus, the CLND opens a new avenue for concentration determinations in the absence of standards of the given analyte (23,24). Moreover, for determination of relative amounts, no standard whatsoever is necessary. All that are needed are the relative CLND peak areas and the molecular formulas of the analytes. Once the relative amounts are found, it is a simple matter to use UV peak areas (e.g., from a UV detector in series with the CLND) to determine the RRFs. Thus, UV response factors (per unit weight) for impurities relative to parent compounds can be determined by means of the following equation ... 

Chiral separations can be considered as a special subset of HPLC. The FDA suggests that for drugs developed as a single enantiomer, the stereoisomeric composition should be evaluated in terms of identity and purity [6]. The undesired enantiomer should be treated as a structurally related impurity, and its level should be assessed by an enantioselective means. The interpretation is that methods should be in place that resolve the drug substance from its enantiomer and should have the ability to quantitate the enantiomer at the 0.1% level. Chiral separations can be performed in reversed phase, normal phase, and polar organic phase modes. Chiral stationary phases (CSP) range from small bonded synthetic selectors to large biopolymers. The classes of CSP that are most commonly utilized in the pharmaceutical industry include Pirkle type, crown ether, protein, polysaccharide, and antibiotic phases [7]. 

A similar CRF may be used for the separation of more than two peaks if it is known that there will always be one critical compound which elutes closest to the main compound of interest. This may be the case for example in a method for determining the purity of a compound when there is one impurity which is very closely structurally related to the compound of interest and therefore much more difficult to resolve from the peak for the main component of the sample than anything else. In other cases, however, it may be equally important to separate all the components from one another. In such instances there must be a high weighting on solutions where the number of peaks observed is the same as the number of components in the sample. Another feature of such examples is that when experimental variables are changed, the elution order of the compounds may change. In some optimisation procedures this is ignored but more frequently the peaks are tracked . This may be done, for... 

There are different issues involved in the LC purity determination of compounds used in foodstuffs. For example since the compounds themselves do not bring about powerful pharmacological effects, there is less likelihood of structurally-related impurities being highly toxic. In principle, it may be possible to carry out less stringent testing for method specificity. However the analyst needs to be wary of the possible presence of toxic non-structurally-related contaminants present. 

As alluded to earlier, the important impurities in food components may well not be structurally related. Accordingly, this presents a difficulty unless there is prior knowledge of the types of impurity likely to be present and their physicochemical properties, the impurities may go undetected through unsuitable choice of LC conditions and/or detector type. 

The size of the TE column can be as small as 2-3 mm X 10-25 mm. It simply has to have sufficient capacity to capture all, or a major percentage, of the components of interest. It should be remembered that a TE column usually captures structurally related compounds and, perhaps, some impurities hence, it might be assumed that only 15-25% of the capacity is taken up by the compound(s) of interest. Because a relatively strong mobile phase is used for backfiushing, band... 

These sialons are structurally related to silicon oxynitride, Si2N20, and have the composition Si2-xAlxO +xN2-x, where x varies from zero to ca. 0.4. Over the whole composition range the Al spectra show a tetrahedral AIO4 resonance at 65 ppm, and in many cases a minor octahedral peak at ca. 2 ppm which is attributed to an impurity phase (Figure 5.35C) (Sjdberg et al. 1992). 

Subra P, Boissinot P, Benzaghou S. Precipitation of pure and mixed cafleine and anthracene by rapid expansion of supercritical solutions. Proceedings of the 5th Meeting on Supercritical Fluids, Nice, France, 1998 1 307-312. Vemavarapu C, Mollan MJ, Needham TE. Co-crystallization of pharmaceutical actives and their structurally related impurities by the RESS process. AAPS Pharm Sci 2002 4(4). 

Of these molecular variants, one is the desired product with the desired properties with respect to biological activity and efficacy. Some structurally related variants (referred to as product related ) exhibit similar properties to the desired product and are therefore not considered as impurities. However, there may also be structurally related variants with altered properties with respect to biological activity, efficacy and/ or safety, which must be considered as impurities. In addition to the molecular variants of the protein (or protein-like) product, additional process-related substances may be part of a biotechnological drug substance, e.g., cell culture media, host cell proteins, DNA residuals, solvents, bacteria and/or viruses. This suggests that the determination of purity of these products (which is referred to as purity estimation rather than purity determination ) is a complex analytical issue. A purity estimation consists of both the definition of the heterogeneity of the protein (or proteinlike) product, and the identification and quantitation of product- and process-re-... 

Copolymerization of Vinylene Carbonate with Some Halo-Substituted Olefins. Copolymerization experiments were conducted using trans-dichloro-ethylene, vinylidene chloride, and CTFE since these monomers have a structural relation to the inhibiting impurities discussed above. With frans-dichloro-ethylene, no polymerization occurred, and only oligomers of VCA with a molecular weight of 300 were formed. Like dichlorovinylene carbonate, trans-dichloroethylene acts as an inhibitor, probably through degradative chain transfer by abstraction of a chlorine atom. 

Class 3 impurities Alerting structure, unrelated to parent structure and of unknown genotoxic (mutagenic) potential. Class 4 Impurities Alerting structure, related to the parent Arrive Pharmaceutical Ingredient (API). 

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