Analytical procedures method evaluation

Indeed, after appropriate sample preparation, standards and samples can be spotted or sprayed onto the same plate, thereby providing a rapid and cost-effective analytical procedure to evaluate all sampling times. If an ultraviolet (UV) scanner is used, it is also possible to determine the amount of substance for each sample. Furthermore, the UV scanner sensitivity may be adapted specifically to analyze highly concentrated samples and poorly concentrated ones on the same plate, provided the calibration curve includes the values. As an example. Fig. 1 presents some kinetic data obtained for vitamin K, which is used as an antidote in dogs suffering from anticoagulant rodenticide poisoning [2]. The method was developed on Ci8-coated silica gel plates. Elution was based... 

NIOSH researchers developed an analytical procedure for evaluating the risks associated with various lifting tasks. The method applies to repeated, two-handed lifting tasks for an 8-hour day without increased risk of developing lower back pain (LBP). Based on additional findings, the Revised Lifting Equation (see note 2) updated the initial method published in 1981. The method has limits and does not apply to the following ... 

Spike recoveries on method blanks and field blanks are used to evaluate the general performance of an analytical procedure. The concentration of analyte added to the blank should be between 5 and 50 times the method s detection limit. Systematic errors occurring during sampling and transport will result in an unacceptable recovery for the field blank, but not for the method blank. Systematic errors occurring in the laboratory, however, will affect the recoveries for both the field and method blanks. 

The objective ia any analytical procedure is to determine the composition of the sample (speciation) and the amounts of different species present (quantification). Spectroscopic techniques can both identify and quantify ia a single measurement. A wide range of compounds can be detected with high specificity, even ia multicomponent mixtures. Many spectroscopic methods are noninvasive, involving no sample collection, pretreatment, or contamination (see Nondestructive evaluation). Because only optical access to the sample is needed, instmments can be remotely situated for environmental and process monitoring (see Analytical METHODS Process control). Spectroscopy provides rapid real-time results, and is easily adaptable to continuous long-term monitoring. Spectra also carry information on sample conditions such as temperature and pressure. 

D. L. Massart, A. Dijkstra, and L. Kaufman, Evaluation and Optimisation of Eaboratoy Methods and Analytical Procedures, Elsevier Science Publishing Co., Inc.,... 

The development of MORT was initiated by the U.S. Atomic Energy Commission, and is described in Johnson (1980). MORT is a comprehensive analytical procedure that provides a disciplined method for detennining the causes and contributing factors of major accidents. It also serves as a tool to evaluate the quality of an existing safety program. 

Chase and Long (1997) propose that this conundrum can be eliminated by the use of Zero Reference Materials (ZRMs) in analytical methods development to fully evaluate the method. A ZRM is a product matrix that lacks those nutrient components that are to be assayed, i.e. a blank matrix. The use of a ZRM in method development can and will give a true indication as to how the method will perform as the spiked nutrient levels approach zero. For example, two products. Corn Starch (NIST RM 8432) and Microcrystalline Cellulose (NIST RM 8416), contain very low elemental concentrations and could conceivably serve as real sample blanks or ZRMs in some analytical procedures. 

Evaluation and Optimization of Laboratory Methods and Analytical Procedures. A Survey of Statistical and Mathematical Techniques... 

D. L. Massart, L. Kaufman and A. Dijkstra, Evaluation and Optimization of Laboratory Methods and Analytical Procedures (Techniques and Instrumentation in Analytical Chemistry, Vol, 1), Elsevier, Amsterdam, 1978, 2nd reprint 1984. 

Some analytical methods open possibilities to evaluate more than only one signal (e.g., OES, MS, XRF). In such cases, the relevant signals yAl, yAl>... (the evaluation of each of which corresponds to another analytical procedure, see Fig. 7.1), do have different sensitivities SAAl, SAAl>..., from which the best will be selected, as a rule. 

Perhaps the most discouraging type of deviation from linearity is random scatter of the data points. Such results indicate that something is seriously wrong with the experiment. The method of analysis may be at fault or the reaction may not be following the expected stoichiometry. Side reactions may be interfering with the analytical procedures used to follow the progress of the reaction, or they may render the mathematical analysis employed invalid. When such plots are obtained, it is wise to reevaluate the entire experimental procedure and the method used to evaluate the data before carrying out additional experiments in the laboratory. 

Analytical procedures are classified as being compendial or non-compendial in character. Compendial methods are considered to be valid, but their suitability should be verified under actual conditions of use. To do so, one verifies several analytical performance parameters, such as the selectivity/specificity of the method, the stability of the sample solutions, and evaluations of intermediate precision. 

It is now necessary to discuss in more detail the performance criteria one can use to evaluate different methods and to describe the validation of different analytical procedures so that you can decide whether or not a given method will fulfil your own particular requirements. In many cases, there will be no method which is entirely suitable for your purpose. In such cases, it will be necessary to adapt an existing method. Before use, such an amended method will need to be validated to ensure that the modifications introduced do not produce erroneous results (see Section 4.6). 

Standard analytical procedures were used to evaluate the composition of ingredients. Of the proximate analyses, nitrogen, lipids, and crude fiber were measured by American Oil Chemists Society (AOCS) methods (12) and moisture and ash by Association of Official Analytical Chemists (AOAC) methods (13). Amino acid analyses were performed by gas-liquid chromatography (14) except for tryptophan, which was analyzed colormetrically Tl5). In addition to these assays, certain tests of ingredient safety or spoilage were also performed, which space does not permit to be reported in this paper, to assure that ingredients met accepted standards for food safety (16). 

A comprehensive two-volume Handbook of Chemometrics and Qualimetrics has been published by D. L. Massart et al. (1997) and B. G. M. Vandeginste et al. (1998) predecessors of this work and historically interesting are Chemometrics A Textbook (Massart et al. 1988), Evaluation and Optimization of Laboratory Methods and Analytical Procedures (Massart et al. 1978), and The Interpretation of Analytical Chemical Data by the Use of Cluster Analysis (Massart and Kaufmann 1983). A classical reference is still Multivariate Calibration (Martens and Naes 1989). A dictionary with extensive explanations containing about 1700 entries is The Data Analysis Handbook (Frank and Todeschini 1994). 

Guidance for Industry, Analytical Procedures and Method Validation Chemistry, Manufacturing and Controls Documentation, Draft, August 2000, Center for Drug Evaluation and Research, Center for Biologies Evaluation and Research, FDA, Department of Health and Human Services, 2000. 

Analytical procedures used as part of a registration dossier in Europe, Japan, or the United States of America should be validated according ICH guideline Q2(R1) Validation of Analytical Procedures Text and Methodology. The objective of analytical method validation is to demonstrate that the analytical procedure is suitable for its intended purpose. Depending on the type of analytical procedure, evaluation of different validation parameters is required. The four most common types of analytical procedures described in this ICH guideline are... 

In Table 1, the typical validation parameters required for the different types of analytical procedures are listed. For all these analytical procedures CE might be an appropriate analytical technique. In fact numerous validated CE methods for pharmaceutical analysis have been described in literature during the last decade.In Table 2, an overview is listed of the ICH validation parameters included in several reported CE validation studies. Since chiral purity determination is an important application area of CE methods, this test is listed separately as a specific analytical procedure. In addition, the determination of drug counterions has been included as a separate application. This overview illustrates that in general the required validation parameters are addressed in reported CE validation studies. It should be noted, however, that the validation parameters included in Table 2 are not necessarily evaluated exactly according ICH requirements in the reported references. Many pharmaceutical companies apply a phase-related validation approach in which the depth of validation depends on the clinical phase of development of the product involved. 

During the last few years, a number of specific monographs for different pharmaceutical products have appeared in pharmacopoeias in which CE is prescribed as one of the analytical procedures. Several comparative studies have been reported in which established analytical procedures described in pharmacopoeial monographs were compared with capillary electrophoretic methods or in which CE was evaluated as a valuable additional technique.Based on the results, some analytical procedures have been replaced by CE-based alternative methods in a number of monographs. For other products, CE has been included in the monograph from the initial version onwards. In addition, CE has been applied... 

The ICH guidelines define robustness as The robusmess of an analytical procedure is a measure of its capacity to remain unaffected by small, but deliberate variations in method parameters and provides an indication of its reliability during normal usage.Thus, the robustness of a method is a measure of its capacity to be transferred to another laboratory without affecting the analytical result. A robustness test is the experimental setup applied to evaluate the robustness of the method. The ICH guidelines also state that One consequence... 

The evaluation of robustness should be considered in the development of the assay and will depend on the type of procedure under development. It must show the reliability of a method with respect to deliberate variations in method parameters. If measurements are susceptible to variations in analytical conditions, the analytical conditions should be suitably controlled or a precautionary statement might be included in the procedure. One consequence of the evaluation of robustness may be that a series of system suitability parameters is established to ensure that the validity of the analytical procedure is maintained whenever used. Typical parameters to be tested would be the following sample concentration, sample stability, labeling variability (if applicable), injection variability, reagent lot-to-lot variability, and capillary vendor. 

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