Limitations of the Technique

The concentration of is determined by measurement of the specific P-activity. Usually, the carbon from the sample is converted into a gas, eg, carbon dioxide, methane, or acetylene, and introduced into a gas-proportional counter. Alternatively, Hquid-scintiHation counting is used after a benzene synthesis. The limit of the technique, ca 50,000 yr, is determined largely by the signal to background ratio and counting statistics. 

Polarisation resistance This technique, sometimes referred to as linear polarisation resistance (LPR), has been applied widely in industrial monitoring because of its ability to react instantaneously to a corrosion situation or change in corrosion rate " " . The limitation of the technique arises from the necessity to have a defined electrolyte as the corrosive (the author has seen an LPR probe installed in a dry gas-line in an oil refinery). 

Fig. 7a, b. PMIM-image of (a) a poly-p-bromostyrene surface [118], (b) a PS/polybutadiene diblock copolymer, PS-b-PB, at approximately 100 fold magnification. The lateral resolution is of the order of 1 pm while the height resolution is of the order of 0.6 nm. The root-mean-square roughness averaged over the area shown is 0.8 nm in (a) close to the resolution limit of the technique. It is much larger (10 nm) in (b) due to the formation of steps after annealing. The scale in z-direction in (a) and (b) is different by a factor of 7... 

The technique as we have described it works only for polar molecules, because only they can interact with microwave radiation. However, variations of these spectroscopic methods can be used to investigate nonpolar molecules, too. A major limitation of the technique is that only the spectra of simple molecules can be interpreted. For complex molecules, we use solid samples and x-ray diffraction techniques. 

The great advantage of Mossbauer spectroscopy is that it can be applied in situ. The major limitation of the technique is that it can only be applied to a couple of elements, among which iron and tin are the easiest to study. 

References 4 and 5 discuss further detail on quantitative frequency assessment, as well as the advantages and limitations of the techniques. Some specific determinations to be made for releases of flammable materials might include the following ... 

N and 0, in solid material. The second point is that EXELFS is especially suitable for the study of inhomogeneous samples (structurally and compositionally heterogeneous in the sense discussed in section 2.2 above) because the primary electron beam can be focussed to a diameter of ca 20. Other advantages of EXELFS have been discussed elsewhere (60, 61). The limitations of the technique include (i) the need to select an optimal thickness of sample so as to minimize multiple scattering and (ii) the susceptibility of the samples to suffer radiation damage. 

Concentration of an analyte prior to measurement may be necessary where the level is likely to be close to or below the practical detection limit of the technique to be used. Solvent extraction, solid phase extraction and ion-exchange may be used for this purpose. Where a complex... 

Solutions to practical problems rarely depend upon a single technique or a single approach. The following example of an impurity identification in a pharmaceutical product illustrates the key role that LC-MS can play in such an investigation, but also illustrates the limitations of the technique. The identification of this impurity has been published elsewhere in complete detail [75]. The problem and solution is summarized here. The impurity, designated as H3, was observed at 0.15% in a bulk lot of the drug substance in the structure below. The impurity required identification before the bulk lot could be released for use in further studies. 

The advantages of the study of the NMR spectroscopy of solutes dissolved in liquid crystal solvents for structural studies have been exploited extensively despite the well-known limitations of the technique, and many compounds have been studied89,90. 

When such investigation is technically possible, as shown in the examples of MAbs and CD40L, MS analysis of complete molecules is fast, powerful, and the method of choice to obtain detailed characterization information. Such a technique should be among the first to be applied for the study of a therapeutic protein. Limitations of the technique include lack of resolution of heterogeneous mixtures and lack of interpretation of isobaric structures, identical in mass but molecularly distinct. The first point can be overcome by reduction of heterogeneity... 

This chapter will explore the relationship of thermodynamic and kinetic data as it pertains to characterizing the stability of various protein systems in the liquid state. Finally, from the wealth of information generated over the past few decades, it should be possible to assess the practical use of microcalorimetry for predicting stability. This technique used in combination with several other bio-analytical methods can serve as a powerful tool in the measurement of thermodynamic and kinetic phenomena.3-9 Attention will be given to limitations of the technique rendered from different applications as well as to areas where it is advantageous. Ultimately, the practical utility of this technique will rest with those familiar with the art. 

In the application of XAS to the study of fuel cell catalysts, the limitations of the technique must also be acknowledged the greatest of which is that XAS provides a bulk average characterization of the sample, on a per-atom basis, and catalyst materials used in low temperature fuel cells are intrinsically nonuniform in nature, characterized by a distribution of particle sizes, compositions, and morphologies. In addition, the electrochemical reactions of interest in fuel cells take place at the surface of catalyst par-... 

Human data and their relevance have to be assessed carefully on a case-by-case basis due to limitations of the techniques available. In particular, attention should be paid to the adequacy of the exposure information, confounding factors, and to sources of bias in the smdy design. The statistical power of the test may also be considered. 

Based on the 96-well format, OCT-PAMPA was proposed and has proved its ability to determine (indirectly) log Poet [87]. PAM PA is a method, first developed for permeability measurements, where a filter supports an artificial membrane (an organic solvent or phospholipids) [88, 89]. With this method, the apparent permeability coefficient (log P ) of the neutral form of tested compounds is derived from the measurement of the diffusion between two aqueous phases separated by 1-octanol layer (immobilized on a filter). A bilinear correlation was found between log Pa and log Poct> therefore log Poet of unknown compounds can be determined from log Pa using a calibration curve. Depending on the detection method used a range oflog P within —2 to +5 (with UV detection) and within —2 to +8 (with LC-MS detection) was successfully explored. This method requires low compound amounts (300 pi of 0.04 mM test compound) and, as for the previous method, samples can be prepared in DM SO stock solutions. For these experiments, an incubation time of 4h was determined as the best compromise in term of discrimination. The limitation of the technique lies in the lower accuracy values... 

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