Method validation influence

Sinkers can significantly influence the dissolution profile of a drug. Therefore, the use of sinkers should be part of the dissolution method validation. If equivalent sinkers are identified during the sinker evaluation and validation, the equivalent sinkers should be listed in the written dissolution test procedure. When a dissolution method utilizes a dissolution sinker and is transferred to another laboratory, the receiving laboratory should duplicate the validated sinker design(s) as closely as possible. 

The method validation procedure should always be documented in order to give evidence of method performance. Proper documentation has an influence on the consistency and subsequent reproducibility, which, at the final stage affect the uncertainty contribution. The information in the validation documents should be clear and easily understood by everyone who uses the method. 

The roles of method validation in the achievement of reliable results are (1) to include all possible effects or factors of influence on the final result, (2) to make them traceable to stated references [reference methods, reference materials, or International System of Units (SI)], and (3) to know the uncertainties associated with each of these effects and with the references. Validation is thus a tool to establish traceability to these references [2,4]. In this context, it is important to see the difference between traceability and accuracy. A method which is accurate, in terms of true (i.e., approximating the true value), is always traceable to what is considered to be the true value. The opposite however is not correct. A method that is traceable to a stated reference is not necessarely true (accurate). Errors can still occur in this method, depending on the reference [12]. 

Before an optimized method can be used in routine analysis, it has to be shown that the method is capable of doing what it is claimed to method validation). Before starting with method validation often a robustness or ruggedness test is performed. In a robustness/ruggedness test (Section 6.6) one evaluates the influence of small variations in the procedure on the performance of the method. These small variations are deliberately introduced and represent variations that could occur when a method... 

Specificity which is classically evaluated in method validation was neglected due to the high specificity of stripping voltammetry and the use of standard addition method. In this work, robustness is not taken into account since standard addition method is considered to reduce the influence of parameters (temperature, ionic strength. ..) on... 

RMs represent an important tool for demonstrating the traceability of analytical measurements to given references. One should keep in mind that the traceability of chemical analyses is often more difficult to demonstrate than for physical measurements. This is due to major differences in the measurement processes (e.g., matrix influence on chemical analyses, various analytical problems linked to the analytes and the methods used, need for sample pretreatment, etc.). Contrary to physical measurements, the calibrants and CRMs used for chemical analyses are not only used for instrument calibration but also for a variety of other purposes (e.g., method validation). In terms of traceability, the theory implies that the certified values of a substance in a CRM should be traceable to the amoimt of the given substance expressed according to the relevant SI unit, i.e., the mol. Since there is no reference mol , this traceability can be established only in relation to the mass SI unit, i.e., the kg. 

Analysis of oral fluid as an alternative matrix to blood and urine in DUID testing offers many advantages. Developments in LC—tandem MS systems have permitted the practical realization of these advantages. The current limitations of ionization source technology means that the robustness of the associated methodology is greatly influenced by matrix effects, and it is essential that this is adequately investigated as part of the method validation. 

Principles and Characteristics Whereas parameters most relevant to method development are considered to be accuracy, system precision, linearity, range, LOD, LOQ, sensitivity and robustness, method validation parameters are mainly bias, specificity, recovery (and stability of the analyte), repeatability, intermediate precision, reproducibility and ruggedness. However, method development and validation are highly related. Also, validation characteristics are not independent they influence each other. Acceptance criteria for validation parameters should be based on the specification limits of the test procedure. Quantitation and detection limits need a statement of the precision at their concentration levels. Procedures used for validation of qualitative methods are generally less involved than those for quantitative analytical methods. According to Riley [82], who has discussed the various parameters for validation of quantitative analytical methods, the primary statistical parameters that validate an analytical method are accuracy and precision. 

Validation of analytical methods has served as the subject of several books. The descriptions in this section are far from exhaustive The aim is to explain the concepts of validation to novices in method development because experience with analytical validation methods can influence method set-up. For example, a user confronted with repeatability or robustness issues during an analytical validation can reconsider his choices of sample preparation, ionization mode, or detection mode during the development of a further method. 

In the first example of applications of the theory in this chapter, we made a point with respect to the polarizability of molecules and showed how the problem could have been handled by the RISM-SCF/MCSCF theory. However, the current level of our method has a serious limitation in this respect. The method can handle the polarizability of molecules in neat liquids or that of a single molecule in solution in a reasonable manner. But in order to be able to treat the polarizability of both solute and solvent molecules in solution, considerable generalization of the RISM side of the theory is required. When solvent molecules are situated within the influence of solute molecules, the solvent molecules are polarized differently depending on the distance from the solute molecules, and the solvent can no longer be neat. Therefore, the polarizable model developed for neat liquids is not valid. In such a case, solvent-solvent PCF should be treated under the solute... 

Elutriation differs from sedimentation in that fluid moves vertically upwards and thereby carries with it all particles whose settling velocity by gravity is less than the fluid velocity. In practice, complications are introduced by such factors as the non-uniformity of the fluid velocity across a section of an elutriating tube, the influence of the walls of the tube, and the effect of eddies in the flow. In consequence, any assumption that the separated particle size corresponds to the mean velocity of fluid flow is only approximately true it also requires an infinite time to effect complete separation. This method is predicated on the assumption that Stokes law relating the free-falling velocity of a spherical particle to its density and diameter, and to the density and viscosity of the medium is valid... 

Bagal (1974) studied the influence of substituents on the ground and first excited states of arenediazonium ions. With regard to compounds in which mesomeric structures such as 4.1b are important, these authors are skeptical about the validity of the PP method. Later, Bagal et al. (1982) used CNDO/2. The calculated 7r-electron densities at all the nitrogen and carbon atoms were similar to those in the earlier PP results. 

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