Method specificity study

The specificity tests depend on the type and purpose of the method. If a specific method is being validated, an interference study should be undertaken. In the case above of the analysis of citric acid and sodium citrate, all other ingredients except microcrystalline cellulose and carboxymethyl cellulose sodium should be chromatographed separately. The known impurities related to memetasone furoate, if available, should be injected as well as the diluting solvent. Interference from filters is required. For nonspecific methods, specificity studies must be determined on a case-by-case basis. For example, the determination of molar ratio of citric acid and sodium citrate by pH in Nasonex should be designed to exclude any other contribution of acidity from other ingredients. 

Heat and humidity are often combined to determine the sensitivity of the API and product, packaged and unpackaged, to these stress conditions. For example studies at 40°C/75% RH and at 50 or 60°C are typically part of a stability program and can also be used to facilitate method specificity studies. Pre-formulation compatibility studies in which the API is combined with various excipients with and without moisture addition and stored at stress conditions may also be helpful in establishing forced degradation conditions for studying method specificity. 

Researchers at the MoneU Center (Philadelphia, Pennsylvania) are using a variety of electrophysical and biochemical techniques to characterize the ionic currents produced in taste and olfactory receptor cells by chemical stimuli. These studies are concerned with the identification and pharmacology of the active ion channels and mode of production. One of the techniques employed by the MoneU researchers is that of "patch clamp." This method aUows for the study of the electrical properties of smaU patches of the ceU membrane. The program at MoneU has determined that odors stimulate intraceUular enzymes to produce cycUc adenosine 3, 5 -monophosphate (cAMP). This production of cAMP promotes opening of the ion channel, aUowing cations to enter and excite the ceU. MoneU s future studies wiU focus on the connection of cAMP, and the production of the electrical response to the brain. The patch clamp technique also may be a method to study the specificity of receptor ceUs to different odors, as weU as the adaptation to prolonged stimulation (3). 

An analytical method vahdation study should include demonstration of the accuracy, precision, specificity, limits of detection and quantitation, linearity, range, and interferences. Additionally, peak resolution, peak tailing, and analyte recovery are important, especially in the case of chromatographic methods (37,38). 

Photoinitiation is an excellent method for studying the pre- and posteffects of free radical polymerization, and from the ratio of the specific rate constant (kx) in non-steady-state conditions, together with steady-state kinetics, the absolute values of propagation (kp) and termination (k,) rate constants for radical polymerization can be obtained. 

Electric-field-driven transport in media made of hydrophilic polymers with nanometer-size pores is of much current interest for applications in separation processes. Recent advances in the synthesis of novel media, in experimental methods to study electrophoresis, and in theoretical methodology to study electrophoretic transport lead to the possibility for improvement of our understanding of the fundamentals of macromolecular transport in gels and gel-like media and to the development of new materials and applications for electric-field-driven macromolecular transport. Specific conclusions concerning electrodiffusive transport in polymer hydrogels include the following. 

The Volta potential is defined as the difference between the electrostatic outer potentials of two condensed phases in equilibrium. The measurement of this and related quantities is performed using a system of voltaic cells. This technique, which in some applications is called the surface potential method, is one of the oldest but still frequently used experimental methods for studying phenomena at electrified solid and hquid surfaces and interfaces. The difficulty with the method, which in fact is common to most electrochemical methods, is lack of molecular specificity. However, combined with modem surface-sensitive methods such as spectroscopy, it can provide important physicochemical information. Even without such complementary molecular information, the voltaic cell method is still the source of much basic electrochemical data. 

In such a case, based on the results of a collaborative study, a content is assigned to the corresponding reference substance which is method specific, i.e. it is only to be used with the method described in the monograph. The establishment of these substances is described in more detail later in the Chapter. 

The laboratory of the European Pharmacopoeia applies the method specific approach (inter-laboratory study) as has been previously described (Technical Guide for the Elaboration of Monographs 1996). 

A range of biomarkers (biological markers) have been developed for the detection of microorganisms using both their genetic (DNA and RNA) and biochemical components. Most methods have originated from studies on pure isolates and have been adapted to identify and quantify either the total or a sub.set of the microbial biomass in a sample. In these methods,. specific taxonomic or pheno-... 

In the sections below, we describe several studies in which flat-histogram methods were used to examine phase equilibria in model systems. The discussion assumes the reader is familiar with this general family of techniques and the theory behind them, so it may be useful to consult the material in Chap. 3 for background reference. Although the examples provided here entail specific studies, their general form and the principles behind them serve as useful templates for using flat-histogram methods in novel phase equilibria calculations. 

This technique has been described as a general method of studying protein-protein interactions as well as a method for investigating the three-dimensional structure of individual proteins (Muller et al., 2001 Back et al., 2003 Dihazi and Sinz, 2003 Sinz, 2003 Sinz, 2006). It also has been used for the study of the interactions of cytochrome C and ribonuclease A (Pearson et al., 2002), to investigate the interaction of calmodulin with a specific peptide binder (Kalkhof et al., 2005a Schmidt et al., 2005), and for probing laminin self-interaction (Kalkhof et al., 2005b). 

Neither the mechanism of absorption nor the mechanism of distribution for hexachloroethane has been established. There are indications that free radical reactions may be responsible for some of the toxic effects of hexachloroethane in the liver (Town and Leibman 1984), but the data are not conclusive. When additional data on absorption, distribution and mechanism are available, compound-specific studies on methods for mitigation of toxic effects can be designed. 

No specific studies have been reported on the application of theoretical methods to these ring systems since CHEC-11(1996) <1996CHEC-II(8)95>. 

A site specific study is the most comprehensive approach. Site specific studies to identify and quantify explosion hazards are usually conducted by the owner s process safety specialist or by specialty consultants. There are several steps which need to be taken, each of which may be done in a variety of ways. The steps are outlined below with some of the available methods. More detailed information is available in CCPS Building Guidelines and API RJ -752. 

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