Analytical methodology types

The strict regulations of the pharmaceutical industry have a significant effect on the quality control of final products, demanding the use of reliable and fast analytical methods. The capacity that the technique has for the simultaneous determination of several APIs with no need of, or with minimum, sample preparation has considerably increased its application in pharmaceutical analytical control. The main limitation of NIR is the relatively low sensitivity that limits the determination of APIs in preparations when their concentration is less than 0.1%. Nevertheless, instrumental improvements allow the determination below this limit depending on the nature of the analyte and the matrix, with comparable errors to the ones obtained with other instrumental techniques. The reference list presents an ample variety of analytical methodologies, types of samples, nature of analyte and calibration models. A detailed treatment of each one is beyond the scope of... 

The most common final separation techniques used for agrochemicals are GC and LC. A variety of detection methods are used for GC such as electron capture detection (BCD), nitrogen-phosphorus detection (NPD), flame photometric detection (FPD) and mass spectrometry (MS). For LC, typical detection methods are ultraviolet (UV) detection, fluorescence detection or, increasingly, different types of MS. The excellent selectivity and sensitivity of LC/MS/MS instruments results in simplified analytical methodology (e.g., less cleanup, smaller sample weight and smaller aliquots of the extract). As a result, this state-of-the-art technique is becoming the detection method of choice in many residue analytical laboratories. 

For a proper understanding of the protein binder s function in artworks and historical building materials, it is essential to identify the individual proteinaceous additives and to distinguish them even in materials where they are present in very small amounts, in insoluble forms and often in matrices unsuitable from an analytical point of view. For many materials the appropriate analytical methodology has not been found up to now and, in general, this type of analyses has not become a routine technique. Thanks to the recent development of proteomics (Section 6.2) most of the afore-mentioned problems have been resolved mass spectrometry forms a fundamental platform for this new methodology. 

Analytical methodologies, which allow the determination of various surfactants and identification of new metabolites are discussed, especially in Chapter 2. The use of multistep sample preparation methods together with advanced techniques like LC-MS (including various types of interfacing systems) for the final identification of surfactants is described in Chapters 3 and 4. Chapter 5 covers the degradation pathway of the major surfactants, which has been studied... 

A variety of smaller multifunctional oxygenated compounds are also found as products of the gas-phase OH-aromatic reactions. Table 6.17 shows the yields of the smallest dicarbonyl compounds from these reactions, which, while small, are not insignificant. In addition to these products, a variety of other multifunctional compounds are typically found, the numbers, types, and concentrations of these products depending on the analytical methodologies used, the reaction conditions, and the skill and imagination of the experimentalist Table 6.18, for example, shows some products observed in the photooxidation of toluene in air where the loss is due to attack by OH (Dumdei et al., 1988). In this particular study, 44% of the reacted toluene could be accounted for by the products shown in Table 6.18. 

GC-M3) is described for characterization of particulate-bound PAHs in diesel emissions. The term PAH will refer to the parent and alkyl-substituted PAHs. The analytical methodology may also be adaptable to other types of sample matrices. 

Together with the fast development of analytical methodologies, great importance is nowadays attached to the quality of the measurement data. Besides the necessary reporting of any result with its MU and traceability of the results to stated standards or references (Section 8.2.2), a third crucial aspect of analytical methods of whichever type is their status of validation. It is internationally recognized that validation is necessary in analytical laboratories. However, less is known about what is validation and what should be validated, why validation is important, when and by whom validation is performed, and finally, how it is carried out practically. This Chapter has tried to answer these questions. 

The development and improvement of analytical methodologies for mycotoxins has been greatly improved by the increased availability of matrix matched certified reference materials (CRMs) (Boenke, 1995) (Table 11.6). The type of matrix CRMs and concentration of the specified mycotoxin are based on the natural occurrence pattern of the toxin in specific foods and feeds. The recent availability of suitable CRMs, while being a prerequisite for the implementation of regulations and standards, will also be invaluable in many ways for the validation of new methods, solving trade disputes and for harmonising proficiency schemes. 

In the complex process of development of analytical methodology for the indirect assessment of exposure to pesticides, one of the first questions to be addressed, concerns what compound(s) to look for and in what sample type. In most cases the parent pesticide will be transformed to a more polar metabolite. 

When dealing with human tissues, experimental dosing or feeding is not possible. Determination of pesticides in human samples taken from individuals poisoned or occupationally exposed can provide information useful in development of analytical methodology. These types of samples may contain biologically incorporated pesticides and metabolites. If human tissue samples containing the pesticides of interest are not available, the researcher must rely on animal models for establishing recovery data for pesticides and metabolites. 

Two of the analytical methodologies that are commonly used to assist in this process have the acronyms STEEP and SWOT. STEEP, which stands for Sociological, Technological, Economic, Environmental and Political, is an extended version of PEST, both of which involve the analysis of these key drivers in a specific location or on a global scale depending on the type of organisation concerned. A brief example of some of the components of a typical PEST analysis is shown in Table Cl. 

Several types of bias are common in analytical methodology, including laboratory bias and method bias. Laboratory bias can occur in specific laboratories, due to an uncalibrated balance or contaminated water supply, for example. This source of bias is discovered when results of interlaboratory studies are compared and statistically evaluated. Method bias is not readily distinguishable between laboratories following a standard procedure, but can be identified when reference materials are used to compare the accuracy of different methods. The use of interlaboratory studies and reference materials allows experimentalists to evaluate the accuracy of their analysis. 

Knowing which factors contribute to the overall variability it should be possible to improve the analytical methodology. The whole error (first condition) is composed of the systematic error (or bias), unspecified random errors, and a series of errors produced during chemical or physical analyses. Uncertainty, also expressed as standard deviation (type A uncertainty), is a concept for measuring the quality of the analytical procedures (Taylor and Kuyaat, 1994). 

Table 6B.2 summarizes the data available in the literature on peptides contents of musts, wines and related substrates such as autolyzed yeasts obtained under winemaking conditions. This table also shows the fractions studied by the different authors, the type of product, the analytical methodology, the results obtained and the purpose of their research. 

It is interesting to note that aspartic acid and/or asparagine and glutamic acid and/or glutamine form part of the peptides of all the wine fractions of different studies, independently of the type of wine or the analytical methodology employed in the analysis. Serine, threonine, alanine and glycine appear in most of the fractions studied while, lysine, tyrosine, valine, leucine, histidine and isoleucine has been found in a minor extent in these fractions. 

The types of information required largely determine the choices of analytical methodology available. Pharmacokinetic studies for new chemical entities... 

For all types of chemical analysis, the quality of the results ultimately relates to the chemical purity of the best available SRM. For naturally chiral substances, there is the additional more serious concern over what constitutes absolute enantiomeric purity. Not even mass spectroscopy, which provides assurance that a substance is chemically pure, can be used to report absolute enantiomeric purities. To actually report an enantiomeric purity higher than 99% is truly beyond the capability of current analytical methodology. ° As noted previously, the fact is that results are measured relative to an enantiopurity defined to be 100%. Chemical purities aside, the measurement of enantiomeric purity and enantiomeric excess is technically the same, the difference being the extent of race-mization. There are only two experimental options, either enantiomeric separations or multivariate spectroscopic analyses, that involve either two distinct detectors or multiple-wavelength detection for a single detector, as noted above. The newly described derivati-zation reactions fulfill the second option. 

Analytical chemistry deals with methods for determining the chemical composition of samples. A compound can often be measured by several methods. The choice of analytical methodology is based on many considerations, such as chemical properties of the analyte and its concentration, sample matrix, the speed and cost of the analysis, type of measurements i.e., quantitative or qualitative and the number of samples. A qualitative method yields information of the chemical identity of the species in the sample. A quantitative method provides numerical information regarding the relative amounts of one or more of the species (the analytes) in the sample. Qualitative information is required before a quantitative analysis can be performed. A separation step is usually a necessary part of both a qualitative and a quantitative analysis. 

---