Impurities, trace level

Anhydrous, monomeric formaldehyde is not available commercially. The pure, dry gas is relatively stable at 80—100°C but slowly polymerizes at lower temperatures. Traces of polar impurities such as acids, alkahes, and water greatly accelerate the polymerization. When Hquid formaldehyde is warmed to room temperature in a sealed ampul, it polymerizes rapidly with evolution of heat (63 kj /mol or 15.05 kcal/mol). Uncatalyzed decomposition is very slow below 300°C extrapolation of kinetic data (32) to 400°C indicates that the rate of decomposition is ca 0.44%/min at 101 kPa (1 atm). The main products ate CO and H2. Metals such as platinum (33), copper (34), and chromia and alumina (35) also catalyze the formation of methanol, methyl formate, formic acid, carbon dioxide, and methane. Trace levels of formaldehyde found in urban atmospheres are readily photo-oxidized to carbon dioxide the half-life ranges from 35—50 minutes (36). 

The devitrification rate is extremely sensitive to both surface and bulk impurities, especially alkah. Increased alkah levels tend to increase the devitrification rate and lower the temperature at which the maximum rate occurs. For example, a bulk level of 0.32 wt % soda increases the maximum devitrification rate 20—30 times and lowers the temperature of maximum devitrification to approximately 1400°C (101). The impurity effect is present even at trace levels (<50 ppm) and can be enhanced with the addition of alumina. The devitrification rate varies inversely with the ratio of alumina-to-alkah metal oxide. The effect is a consequence of the fact that these impurities lower glass viscosity (102). 

Ethylene oxide is sold as a high purity chemical, with typical specifications shown ia Table 14. This purity is so high that only impurities are specified. There is normally no assay specification. Proper sampling techniques are critical to avoid personal exposure and prevent contamination of the sample with trace levels of water. A complete review and description of analytical methods for pure ethylene oxide is given ia Reference 228. 

The most common application of dynamic SIMS is depth profiling elemental dopants and contaminants in materials at trace levels in areas as small as 10 pm in diameter. SIMS provides little or no chemical or molecular information because of the violent sputtering process. SIMS provides a measurement of the elemental impurity as a function of depth with detection limits in the ppm—ppt range. Quantification requires the use of standards and is complicated by changes in the chemistry of the sample in surface and interface regions (matrix efiects). Therefore, SIMS is almost never used to quantitadvely analyze materials for which standards have not been carefiilly prepared. The depth resoludon of SIMS is typically between 20 A and 300 A, and depends upon the analytical conditions and the sample type. SIMS is also used to measure bulk impurities (no depth resoludon) in a variety of materials with detection limits in the ppb-ppt range. 

Static SIMS is labeled a trace analytical technique because of the very small volume of material (top monolayer) on which the analysis is performed. Static SIMS can also be used to perform chemical mapping by measuring characteristic molecules and fiagment ions in imaging mode. Unlike dynamic SIMS, static SIMS is not used to depth profile or to measure elemental impurities at trace levels. 

Because the beam monitor allows accurate measurement of the total number of ions that are analyzed, a graded series of exposures (i.e., with varying numbers of ions impinging on the plate) is collected, resulting in the detection of a wide range of concentrations, from matrix elements to trace levels of impurities. In Figure 2, the values of the individual exposures have been replaced with the concentration range that can be expected for a mono-isotopic species just visible on that exposure. In this example, exposures from a known Pt sample have been added to determine the response curve of the emulsion. 

The acceptance criterion for recovery data is 98-102% or 95-105% for drug preparations. In biological samples, the recovery should be 10%, and the range of the investigated concentrations is 20% of the target concentrations. For trace level analysis, the acceptance criteria are 70-120% (for below 1 ppm), 80-120% (for above 100 ppb), and 60-100% (for below 100 ppb) [2]. For impurities, the acceptance criteria are 20% (for impurity levels <0.5%) and 10% (for impurity levels >0.5%) [30], The AOAC (cited in Ref. [11]) described the recovery acceptance criteria at different concentrations, as detailed in Table 2. A statistically valid test, such as a /-test, the Doerffel-test, or the Wilcoxon-test, can be used to prove whether there is no significant difference between the result of accuracy study with the true value [29],... 

There has been an increasing global trend in the wire and cable industry to restrict and remove the presence of lead in materials used for insulation and jacketing applications. The various standards that apply to lead in electrical applications are discussed. One of the issues is how to define the low levels of lead. Many minerals contain trace levels of lead as a chemical impurity. These minerals are used in rubber and plastics and thus the final composition is likely to contain trace amounts of lead. With modem analytical techniques, lead can be found at levels lower than five parts per million. Therefore, to satisfy increasing demands on wire and cable materials, a new series of thermoplastic vulcanisates (TPV) has been introduced that contains no added lead chemicals. These TPV materials have recently been granted a UL listing for flexible cord applications. The properties of these materials are presented and highlighted. 6 refs. 

CE is increasingly applied to analysis of proteins present at trace levels in biological materials or to determination of impurities and degradation products in formulations... 

Traditional methodologies for structural identification of trace level impurities in drng substances/products usually involve fractionation of each impurities using a scaled-np analytical chromatographic method, followed by off-line spectroscopic analysis. Coupling of HPLC separation and electrospray mass spectrometry allows on-line acquisition of full scan mass spectra and generation of tandem mass spectrometric data. LC/ESI MS has revolntionized trace analysis for qnalitative and quantitative studies in pharmaceutical analysis. 

D.8.3. Cl Impurity. Trace amounts of chloride impurities, which may be present at levels between 0.1 and 0.5mol/kg, have significant effects on the physical properties of ionic liquids, such as viscosity and density. Increases in viscosity are of particular concern in biphasic processes because of the formation of emulsions that affect the interface between the two phases 88). 

As outlined above displacement chromatography may find its most important uses in the analytical area. The ability to enrich trace levels of components is ideally suited to the proteomics where more powerful tools are desperately needed to address the vast concentration ranges present in order to identify trace components. The technique also offers a way to isolate large quantities of protein variants which is important for the identification and characterization of minor product-related impurities commonly associated with therapeutic proteins. 

Norwood DL, Qiu F. Strategies for the analysis of pharmaceutical excipients and their trace level impurities. Am Pharma Rev 2004 7(5) 92-99. 

---