Quality of experimental data

It has to be pointed out that prediction failures of general ADME models are often related to two major sources namely the quality of experimental data used to derive the model and the interpretation of the final model. These problems are discussed in depth by Stouch et al. (2003). Some models fail as they were built from data collected from different sources and laboratories. Although this might work for some robust standardized ADME assay, it could produce incomparable data for others. Such problems have been reported for example for Caco-2 assays from different laboratories. Even if the experimental... 

This paper is devoted to the verification of the quality of experimental data regarding the solubility of sparingly soluble solids, such as drugs, environmentally important substances, etc. in mixed solvents. A thermodynamic consistency test based on the Gibbs-Duhem equation for ternary mixtures is suggested. This test has the form of an equation, which connects the solubilities of the solid, and the activity coefficients of the constituents of the solute-free mixed solvent in two mixed solvents of close compositions. 

The very existence of the powder diffraction pattern, which is an experimentally measurable function of the crystal structure and other parameters of the specimen convoluted with various instrumental functions, has been made possible by the commensurability of properties of x-rays and neutrons with properties and structure of solids. As in any experiment, the quality of structural information, which may be obtained via different pathways (two possibilities are illustrated in Figure 2.62 as two series of required steps), is directly proportional to the quality of experimental data. The latter is usually achieved in a thoroughly planned and well executed experiment as will be detailed in Chapter 3. Similarly, each of the data processing steps, which were described in this chapter and are summarized in Figure 2.62, requires knowledge, experience and careful execution, and we will describe them in practical terms in Chapters 4 through 7. 

In modem diffractometers both scanning modes result in nearly identical quality of experimental data. A step scan is usually considered as the one with less significant positioning errors, which could be important in experiments where the maximum lattice parameter precision is essential. Continuous scans are used most often for fast experiments, whereas step scans are usually employed in overnight or weekend experiments. 

This figure of merit is different from the so-called expected residual used to quantify the quality of experimental data in a Rietveld refinement. The latter is given as... 

A simple analysis of Eqs. 6.18 to 6.20 and 6.22 indicates that a better fit results in lower values of all residuals. Unfortunately, there are no exact thresholds for Rp, R p and/or Rb, below which a fit is acceptable, good or excellent. To a certain degree, the absolute quality of the result is established by the relationship between Rwp and Rexp, i.e. by the value of The expected residual (Eq. 6.21) characterizes the quality of experimental data because a larger denominator means a better counting statistics (see... 

Refinement of the crystal structure is, therefore, a powerful chemical analysis technique. Unlike conventional chemical analysis, which only yields the bulk composition of the sample, powder diffraction analysis facilitates accurate determination of the occupancies of different crystallographic sites by various chemical elements, or in other words, establishes precise chemical composition of the crystal at the atomic resolution. It should be noted that the results may be considered reliable only when the difference in the scattering ability of atoms in question is significant, in addition to a very high quality of experimental data. This is indeed the case here because scattering factors of Sn and Ni are related as-1.8 1. 

Experimental data reveal that the corrosivity of the test cabinet is greatly influenced by the procedure of performance, and by design parameters of the test cabinet. The quality of hydrochloric acid, used for the corrosion product stripping, as well as the other parameters of used materials, which should be checked by additional experiments, influence greatly the quality of experimental data too. 

The quality of experimental data can be assessed before regression by a test for thermodynamic consistency. The treatment is based on the Gibbs-Duhem equation written here as ... 

Intersection point analysis is much less dependable on the quality of experimental data than the first two criteria, and the Haldanes are reaUy the same for... 

Validation of the models on the basis of experimental results is extremely important. First of all, the complexity of the model has to be compatible with the quality of experimental data available. Crude data with high noise level may identify only rather crude models. A proper interplay between experimental and modelling work is crucial. 

In general, such differential methods of the kinetic data determination are very sensitive to the quality of experimental data, especially to the determination of instantaneous rates, a and the related differences, A. For this reason, and in view of the inaccuracy of this determination in the initial and final reaction stages, they are not so extensively used. However, on rearrangement and upon assuming constant values of a and/or a the following ratio is found useful for another direct estimation of E from several parallel measurements by the so-called iso-conversional and iso-rate cross sections, as introduced (and often labeled) by Flynn and Ozawa [503,504] (a = const Alna/A(l/T) = E/R = Ain Z f(oc)/A In (1/T) (<= a = const). 

In this section, we explore the relationship between the activity coefficients of the different species in a mixture. Using the Gibbs-Duhem equation, we will show that the activity coefficients are not independent. Their interrelationship will motivate development of a new type of thermodynamic property—excess Gibbs energy. Finally, we will illustrate an application of these principles by coming up with a way to test the quality of experimental data and see whether they are thermodynamically consistent. 

The Gibbs-Duhem equation provides a general relation for the partial molar properties of different species in a mixture that must always be true. For example, we just saw how the activity coefficient of different species can be related to one another. In this section, we explore one way to use this interrelation to judge the quality of experimental data. The basic idea is to develop a way to see whether a set of data conform to the constraints posed by the Gibbs-Duhem equation. If the data reasonably match, we say they are thermodynamically consistent. On the other hand, data that do not conform to the Gibbs-Duhem equation are thermodynamically inconsistent and should be considered unreliable. The development that follows is based on the relation between activity coefficients in a binary mixture of species a and b. It serves as an example to this methodology there are several other ways that have been developed to apply this same type of idea. 

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