Trace metal impurities

As opposed to gaseous, pure formaldehyde, solutions of formaldehyde are unstable. Both formic acid (acidity) and paraformaldehyde (soHds) concentrations increase with time and depend on temperature. Formic acid concentration builds at a rate of 1.5—3 ppm/d at 35°C and 10—20 ppm/d at 65°C (17,18). Trace metallic impurities such as iron can boost the rate of formation of formic acid (121). Although low storage temperature minimizes acidity, it also increases the tendency to precipitate paraformaldehyde. 

Benzyl chloride undergoes self-condensation relatively easily at high temperatures or in the presence of trace metallic impurities. The risk of decomposition during distillation is reduced by the use of various additives including lactams (43) and amines (44,45). Lime, sodium carbonate, and triethylamine are used as stabilizers during storage and shipment. Other soluble organic compounds that are reported to function as stabilizers in low concentration include DMF (46), arylamines (47), and triphenylphosphine (48). 

The technique can be used to measure concentrations in the range 10 6-10 9M and as such is eminently suitable for the determination of trace metal impurities of recent years it has found application in the analysis of semiconductor materials, in the investigation of pollution problems, and in speciation studies. 

The above reaction is catalyzed by copper and other trace metal impurities and can be prevented by adding a suitable complexing agent. In a modification of the Raschig process, what is known as Olin-Raschig process, liquid chlorine feed is continuously absorbed in dilute NaOH solution forming sodium hypochlorite which, similar to the Raschig process, is made to react with... 

Numerous applications concern the mass spectrometric analysis of quite different gases and highly volatile compounds. For example, the determination of trace metal impurities in ethylene gas for... 

The cleaning of the various catalyst samples has to be scrutinized for each material studied. For iron for example, the major impurity is sulfur, and its removal must be carried out outside the vacuum system in a furnace in a constant hydrogen flow for a long period of time (days). Trace metallic impurities or nonmetallic impurities may be removed either by argon ion bombardment in the vacuum chamber or by chemical treatment using gas-surface interactions of different types. 

In our next series of measurements we determined the effect of pH on the oxidation of H2S in buffered dilute solutions. The measurements were made at S5°C to speed up the acquisition of data. The results are shown in Figure 7. The results from pH = 2 to 8 are similar to the earlier measurements of Chen and Morris (41). Above a pH = 8 we find the rate to be independent of pH unlike the results of Chen and Morris (411 who find a complicated pH dependence. This could be related to trace metal impurities in the buffers used by Chen and Morris (41). Hoffmann and Lim (461 nave examined these trace metal effects and the base catalysis of the oxidation of H2S. 

J. Nawrocki, D. Moir and W. Szczepaniak, Trace metal impurities in silica as a cause of strongly interacting silanols, Chromatographia, 28 143 (1989). 

Trace metal impurities in buffer salts were found to enhance the oxidative degradation of prednisolone (78). Phenylephrine hydrochloride decomposes in the presence of heavy metal ions (79). The autooxidation of procaterol, a sympathomimetic amine, is enhanced in the presence of ferric ions (80). The photodegradation of riboflavin is enhanced by the presence of polysorbate 80 and sodium lauryl sulfate (81). 

The evidence for the hypothesis that initiation of autoxidation involves trace metal impurities and that autoxidation would in fact not occur in the absence of trace metals can be summarized as follows ... 

As far as the general mechanism of electron transfer is concerned, there have been a number of important reviews in recent years (20, 27). This paper has dealt with the limited aspects which involves free radical formation and its consequences, while reviewing some of my work and placing particular emphasis on the importance of the role of trace metal impurities and of sound energetics in the analysis of reaction schemes. 

The silica may also be contaminated by metallic impurities such as aluminum, nickel, and iron, depending on the synthesis of the silica or the manufacturing process. These metals may be present either in the form of oxides and hydrous oxides or through oxygen bonds attached to an Si atom [3]. The metal impurities may also have an effect on the chromatography, causing peak tailing due to complexation with the trace metal impurities. The acidity of the surface silanols is increased with the presence of these metal impurities. 

Trace metal impurities in excipients can lead to oxidative catalysis resulting in drug substance degradation.14 The metals most commonly... 

The reactions may be catalyzed by trace metal impurities such as polymerization catalyst residues or contaminants from processing machinery. The reaction scheme is similar to that in thermal oxidation, differing only in the method of initiation and in the relative reaction rates (which are likely to be quite different at the higher temperatures normally required for thermal initiation). 

It is not within the scope of this chapter to provide a comprehensive discussion of silica gel chemistry. An excellent treatise is available (77). The parameters that most significantly affect bonding chemistries and solute retention properties are surface area, pore volume, pore diameter, trace metal impurities, and thermal pretreatments. Both Sander and Wise (90) and Sands et al. (91) have studied the effect of pore diameter and surface treatment of the silica on bonding reactions. Boudreau and Cooper (92) have studied the effects of thermal pretreatments at 180, 400, and 840°C on the subsequent chemical modification of silica gel, and showed that thermal pretreatment at temperatures >200°C can produce more homogeneous distribution of active silanols which are available for subsequent derivatization. 

Among the various types of atomic spectroscopy, only two, flame emission spectroscopy and atomic absorption spectroscopy, are widely used and accepted for quantitative pharmaceutical analysis. By far the majority of literature regarding pharmaceutical atomic spectroscopy is concerned with these two methods. However, the older method of arc emission spectroscopy is still a valuable tool for the qualitative detection of trace-metal impurities. The two most recently developed methods, furnace atomic absorption spectroscopy and inductively coupled plasma (ICP) emission spectroscopy, promise to become prominent in pharmaceutical analysis. The former is the most sensitive technique available to the analyst, while the latter offers simultaneous, multielemental analysis with the high sensitivity and precision of flame atomic absorption. 

The analytical measurement of elemental concentrations is important for the analysis of the major and minor constituents of pharmaceutical products. The use of atomic spectroscopy in this regard has been the subject of several reviews (2,3,35,36). Metals are major constituents of several pharmaceuticals such as dialysis solutions, lithium carbonate tablets, antacids, and multivitamin-mineral tablets. For these substances, spectroscopic analysis is an important tool. It is indispensable for the determination of trace-metal impurities in pharmaceutical products and the qualitative and quantitative analysis of metals, essential and toxic, in biological fluids and tissues (37). Beyond this, several drugs which do... 

The determination of trace metal impurities in pharmaceuticals requires a more sensitive methodology. Flame atomic absorption and emission spectroscopy have been the major tools used for this purpose. Metal contaminants such as Pb, Sb, Bi, Ag, Ba, Ni, and Sr have been identified and quantitated by these methods (59,66-68). Specific analysis is necessary for the detection of the presence of palladium in semisynthetic penicillins, where it is used as a catalyst (57), and for silicon in streptomycin (69). Furnace atomic absorption may find a significant role in the determination of known impurities, due to higher sensitivity (Table 2). Atomic absorption is used to detect quantities of known toxic substances in the blood, such as lead (70-72). If the exact impurities are not known, qualitative as well as quantitative analysis is required, and a general multielemental method such as ICP spectrometry with a rapid-scanning monochromator may be utilized. Inductively coupled plasma atomic emission spectroscopy may also be used in the analysis of biological fluids in order to detect contamination by environmental metals such as mercury (73), and to test serum and tissues for the presence of aluminum, lead, cadmium, nickel, and other trace metals (74-77). 

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