Method validation general conditions

Differences in the Responses of the Different Types of Models. The basic differences that exist in the heat and mass balances for the different types of models determine deviations of the responses of types I and II with respect to type III. In a previous work (1) a method was developed to predict these deviations but for conditions of no increase in the radial mean temperature of the reactor (T0 >> Tw). In this work,the method is generalized for any values of T0 and Tw and for any kinetic equation. The proposed method allows the estimation of the error in the radial mean conversions of models I and II with respect to models III. Its validity is verified by comparing the predicted deviations with those calculated from the numerical solution of the two-dimensional models. A similar comparison could have been made with the numerical solution of the one-dimensional models. 

Method validation Analytical methods must be shown to give reliable data, free from bias and suitable for the intended use. Most methods are multi-step procedures, and the process of validation generally involves a stepwise approach in which optimized experimental parameters are tested for robustness (ruggedness), that is sensitivity to variations in the conditions, and sources of errors investigated. 

Fidelity in the context of method validation is better known as reproducibility or repeatability. However, each term possesses a precise meaning in terms of quality and fidelity and repeatability should not be confused. The definitions can vary from one field to another and it is important to describe fidelity and repeatability in the documentation of an analytical procedure and detail the conditions of their measure number of samples analyzed, time lapses between samples, and other factors. The definitions below were used by the European pharmaceutical industry at the time of the writing of this chapter. The criteria linked to the fidelity of measures are generally expressed as coefficients of variation (CVs). 

In most situations analysts can achieve a rapid reasonable separation of compounds using an appropriate standard CE method with generic operating conditions [877]. This eliminates or reduces dramatically the need for method development. Major instrumental error sources in CE are detection, integration and injection. General guidelines for validation of CE methods are available and similar to those of HPLC [878]. Validated CE methods often perform the same as, or better than, the corresponding HPLC methods. 

A more general analysis requires the use of two effective permeability coefficients, one for each pH, each of which would be valid in the respective iso-pH conditions. Since fewer limiting assumptions are made, the more general method may be more suitable for high-throughput applications. We continue to derive the appropriate new model. 

It is still unclear how much general validity attaches to the metaphosphate mechanism as formulated for the present variant for the oligonucleotide synthesis. Depending upon the reaction conditions, preparative method, activating reagent, and length of the nucleotide block, other mechanisms may dominate. 

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