Accuracy of a method

The accuracy of a method depends on its selectivity for the analyte. Even the best methods, however, may not be free from interferents that contribute to the measured signal. Potential interferents may be present in the sample itself or the reagents used during the analysis. In this section we will briefly look at how to minimize these two sources of interference. 

Richardson extrapolation can be used to improve the accuracy of a method. Suppose we step forward one step At with a pth-order method. Then redo the problem, this time stepping foi ward from the same initial point, but in two steps of length Af/2, thus ending at the same point. Call the solution of the one-step calculation y and the solution of the two-step calculation yo. Then an improved solution at the new time is given by... 

The accuracy of a method can only be determined if the true answer is known and, of course, for the majority of analyses it is not. The accuracy of a method is determined during its validation procedure by the analysis of samples containing known amounts of analyte. In order to ensure that the method accuracy is maintained during routine use, samples containing known amounts of analyte are analysed among the unknowns as part of a quality control regime [12, 13]. 

Another way to verify the accuracy of a method (I) under validation is the analysis of a given set of test samples with graduated analyte concentrations by both methods, (I), and an independent one (II), which is known to be accurate. The special recovery function in this case is given by Eq. (6.47b). 

The accuracy of an analytical method is given by the extent by which the value obtained deviates from the true value. One estimation of the accuracy of a method entails analyzing a sample with known concentration and then comparing the results between the measured and the true value. The second approach is to compare test results obtained from the new method to the results obtained from an existing method known to be accurate. Other approaches are based on determinations of the per cent recovery of known analyte spiked into blank matrices or products (i.e., the standard addition method). For samples spiked into blank matrices, it is recommended to prepare the sample at five different concentration levels, ranging over 80-120%, or 75-125%, of the target concentration. These preparations used for accuracy studies usually called synthetic mixtures or laboratory-made preparations . 

The accuracy of a method should be assessed using a minimum of nine determinations conducted over a minimum range of three concentration levels (80%, 100%, and 120% of the target concentration) [37]. Experience from our laboratory has showed that by using at least five levels of concentrations in duplicate (i.e., 80%, 90%i, 100%i, 110%, and 120% of the target concentration), a better result can be achieved. For dissolution studies, the accuracy of the required profile should be tested at 40%, 75%, and 110% of the theoretical release) [20],... 

The accuracy of a method is defined as the closeness of the value obtained to known or accepted values. Accuracy can be determined in a number of ways, depending on the nature of the CZE method and availability of orthogonal techniques to compare results. If practical, spike recovery studies (i.e., testing to determine whether recovery matches the amount of a known analyte or impurity spiked) are good alternatives to orthogonal assay comparisons. ICH guidelines also allow method accuracy to be inferred, once specificity, linearity, and precision are established. 

The selection of an appropriate reference material should be based upon the availability of a matrix that is similar to the anticipated routine unknowns. Similarity of chemical matrix and analyte concentrations is particularly important when attempting to assess accuracy of a method that requires destructive sample preparation. 

What factors can be used to predetermine the quality and utility of a method An analyst must consider the following questions Do I need a proximate analytical method that will determine all the protein, or carbohydrate, or lipid, or nucleic acid in a biological material Or do I need to determine one specific chemical compound among the thousands of compounds found in a food Do I need to determine one or more physical properties of a food How do I obtain a representative sample What size sample should I collect How do I store my samples until analysis What is the precision (reproducibility) and accuracy of the method or what other compounds and conditions could interfere with the analysis How do I determine whether the results are correct, as well as the precision and accuracy of a method How do I know that my standard curves are correct What blanks, controls and internal standards must be used How do I convert instrumental values (such as absorbance) to molar concentrations How many times should I repeat the analysis And how do I report my results with appropriate standard deviation and to the correct number of significant digits Is a rate of change method (i.e., velocity as in enzymatic assays) or a static method (independent of time) needed ... 

Accuracy means the closeness of agreement between a test result and the accepted reference value. It is determined by determining trueness and precision [57], In a strict sense, the accuracy of a method is affected by systematic (bias) as well as random (precision) error components, but the term is often used to describe only the systematic error component, i.e., in the sense of bias. In this sense sometimes... 

The simplest way to estimate the accuracy of a method is to analyze reference materials for which there are known values of p for the analyte. Thus, the difference... 

The principal considerations in% choosing a finite-difference method for (7) are accuracy, stability, computation time, and computer storage requirements. Accuracy of a method refers to the degree to which the numerically computed temporal and spatial derivatives approximate the true derivatives. Stability considerations place restrictions on the maxi-... 

It is impossible to conduct an infinite number of extractions of a speciman to determine the accuracy of a method. As a result, we estimate the accuracy of an assay by performing a finite number of extractions (n) on the specimen. We report the accuracy as the mean (x- = Hxifn, i = 1,2,. ..,n) of the multiple determinations, expressed as a percent of the known concentration. The finite group of determinations is a sample from the population, and its mean is referred to as the sample mean. The sample mean is a statistic that estimates the population parameter p. If we could obtain the means from an infinite number of same-size samples, regardless of their size, then the mean of these infinite sample means would equal p. In statistical terminology, we say that the sample mean is an unbiased estimator of the population mean. Unbiasedness is a... 

A primary standard is a highly purified compound that serves as a reference material in volumetric and mass titrimetric methods. The accuracy of a method is critically dependent on the properties of this compound. Important requirements for a primary standard are the following ... 

The accuracy of a method can be determined by performing recovery experiments, implementing standard addition calibration procedures, testing reference materials, etc. It is also possible to compare the test results of a new... 

It is more diflBcult to secure conclusive evidence of the specificity of a chemical method, when applied to a biological system (B7). Since the constituent will almost certainly have to be determined as one component in a mixture, the possible interfering effects of some (ideally all) of these other substances need to be determined, each over the range of concentrations liable to be met with in practice. Whereas the accuracy of a method can best be determined by recovery experiments, which depend on the availability of a pure sample of the compound under investigation, the specificity of a technique and the effects of possible interfering factors can be more readily investigated by experiments involving radioactive isotopes these isotopic assessments of specificity have so far not been widely applied in clinical chemistry. 

In clinical chemistry, the closely controlled reaction conditions of quantitative inorganic and organic chemistry cannot always be obtained, since estimations have to be performed on complex mixtures. This means that both simple aqueous and protein-containing standards have to be considered, and the criteria adopted when choosing a standard for use in clinical chemistry may be unable to meet the criteria of primary standards used in other branches of quantitative chemistry. For some determinations, the accuracy of a method cannot be established at present since pure materials for standardization are not yet available the best examples of such methods are provided by determinations of enzyme activity in serum, but suitable control preparations exist for monitoring the precision of these assays (e.g., H8). 

Accuracy and precision are the most important characteristics of an analytical method they give the best indication of random and systematic error associated with the analytical measurement. Systematic error refers to the deviation of an analytical result from the true value, and therefore affects the accuracy of a method. One the other hand, random errors influence the precision of a method (Kallner et al., 1999). Ideally, accuracy and precision should be assessed at multiple concentrations within the linear range of the assay (low, medium and high concentration). 

Determination The trueness or accuracy of a method can be determined by using it to analyze specially prepared samples. In these, the active ingredient is added in a similar concentration to that expected in the pharmaceutical product and also in somewhat higher and lower concentrations. The accuracy is then calculated as a % recovery. 

We can, by good analytical technique, such as making comparisons against a known standard sample of similar composition, arrive at a reasonable assumption about the accuracy of a method, within the limitations of the knowledge of... 

Accuracy of a method is the closeness of the obtained value to the true value for the sample. This is probably the most difficult parameter to validate. One should consider the sampling and sample treatment, in addition to the measurement method accuracy. Accuracy of the method can be determined in one of three ways. In increasing order of importance, these are ... 

What are the main ways of assessing accuracy of a method ... 

Accuracy of a method of analysis generally is determined by analyzing standards with matrices the same or similar to the samples of interest. These standards have known isotopic abundances and/or concentrations. The limit to this approach often is the accuracy of the reference technique that was used to characterize the standard. 

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