Analytical methods reference intervals

Although glucose can be assayed by several different analytical procedures, reference intervals do not vary significantly among methods. The following values should apply to virtually aU currently used glucose assays. 

Range Ihe range of an analytical method refers to the interval between the upper and lower concentration for which it has been demonstrated that there is a suitable level of accuracy, precision, and linearity Repeatability A measme of the precision of the method over a short period of time using the same sample solution Resistance to mass transfer The time taken for the analyte to transfer from the mobile to the stationary phase... 

Repeatability Repeatability is a measure of the precision under the same operating conditions over a short interval of time, that is, under normal operating conditions of the analytical method with the same equipment. It is sometimes referred to as intra-assay precision. 

You purchased a Standard Reference Material (Box 3-1) coal sample certified by the National Institute of Standards and Technology to contain 3.19 wt% sulfur. You are testing a new analytical method to see whether it can reproduce the known value. The measured values are 3.29, 3.22, 3.30, and 3.23 wt% sulfur, giving a mean of 3r = 3.260 and a standard deviation of, v = 0.04,. Does your answer agree with the known answer To find out, compute the 95% confidence interval for your answer and see if that range includes the known answer. If the known answer is not within your 95% confidence interval, then the results do not agree. 

Analyte levels are compared both to the concomitant control group (using appropriate statistical methods of the group size is large enough) and additionally to laboratory-specific reference intervals for the species, strain, age and sex in question. 

The latter are hence extremely useful to monitor the performance of an analytical method with time by setting up control charts which allow for the statistical control of measurements (33). Reference materials are necessarily homogeneous and stable. If analyzed at regular intervals, quick and clear information can be gained on any tendency for the analytical process to go out of control when the... 

It is often claimed that the analytical quality should be better when determining reference values than when producing routine values. This may be true for accuracy aU measures should be taken to eliminate bias. The question of imprecision is more difficult because it depends partly on the intended use of the reference values. Increases in analytical random variation result in widening of the reference intervals For some special uses of reference values, the narrower reference interval obtained by a more precise analytical method may be appropriate. However, this is usually not true... 

A new requirement of the final CLIA regulations is that laboratories must perform method validation studies oh all new tests introduced after April 24, 2003. Before this, laboratories that implemented new methods and analytical systems that had been cleared by the Food and Drug Administration (FDA) could simply follow manufacturers directions for operation and assume that the manufacturer s performance claims were valid. With the issuance of the final rule, the performance of all new tests must be validated in each laboratory to document the reportable range, precision, accuracy, and reference intervals. For some methods, it may also be necessary to determine the detection limit and to test for possible interferences. 

Analytical Methods and Reference Intervals for Amylase Isoenzymes... 

Systematic error in an analytical method must be determined and corrected for. We have seen that systematic error is assessed by making a measurement on a certified reference material (sometimes just referred to as a CRM). The mean of a number of determinations, x, can be used to decide if the systematic error is significant by using the equation for a confidence interval of the mean... 

Certified values are expected to be correct - with a probability of 95% - within the stated uncertainty intervals. However, certified data alone do not guarantee the successful, i.e. correct application of reference materials. Depending on the material to analyse or on the testing method to be applied, expert assessment and problem-related selection is required. The task-related application of an (instrumental) analytical method including calibration standards still demands professionally trained specialists. 

Therefore, although the physical methods remain the primary methods for determining the photon flux and are still in use in some cases (e.g., to control the relative emission intensity of the lines emitted by the mercury lamps or the transmittance of filters), the most commonly utilized method is based on a chemical actinometer, i.e., a reference substance undergoing a photochemical reaction whose quantum yield, <, is known, calibrated against a physical device or well characterized actinometers. The chemical actinometers are mainly fluid systems (generally solutions) irradiated for a suitable time interval after irradiation, an analytical method allows to determine the number of decomposed molecules by means of the equations reported in Sect. 4.2 it is possible to calculate the number of incident photons. The value so obtained may be used to calculate the quantum yield of other photoreactions, provided that these are... 

Comparison of test values with a conventional true value ( reference value ) of a (certified) reference material (RM, CRM). In method development and validation of analytical procedures, the comparison of experimental results with standards of diverse kind (laboratory standards, certified reference materials, primary standards) plays an essential role. The decision as to whether an experimental result hits the reference value depends not only from the result itself but also from its uncertainty interval. 

The process of providing an answer to a particular analytical problem is presented in Figure 2. The analytical system—which is a defined method protocol, applicable to a specified type of test material and to a defined concentration rate of the analyte —must be fit for a particular analytical purpose [4]. This analytical purpose reflects the achievement of analytical results with an acceptable standard of accuracy. Without a statement of uncertainty, a result cannot be interpreted and, as such, has no value [8]. A result must be expressed with its expanded uncertainty, which in general represents a 95% confidence interval around the result. The probability that the mean measurement value is included in the expanded uncertainty is 95%, provided that it is an unbiased value which is made traceable to an internationally recognized reference or standard. In this way, the establishment of trace-ability and the calculation of MU are linked to each other. Before MU is estimated, it must be demonstrated that the result is traceable to a reference or standard which is assumed to represent the truth [9,10]. 

Measurement uncertainty is the most important criterium in both method validation and IQC. It is defined as a parameter, associated with the result of a measurement, that characterizes the dispersion of the values that could reasonably be attributed to the measurand [14]. The measurand refers to the particular quantity or the concentration of the analyte being measured. The parameter can be a standard deviation or the width of a confidence interval [14, 37]. This confidence interval represents the interval on the measurement scale within which the true value lies with a specified probability, given that all sources of error are taken into account [37]. Within this interval, the result is regarded as being accurate, that is, precise and true [11]. 

This together with Estimates 3.1 and 3.2 also provides the existence of uniform bounds for uxx in all such domains for 0 < t < oo. Analogous arguments demonstrate the uniform boundedness of uxxx which is sufficient for a reference to Gevrey s results [32]. All stated above proves that the length of any interval of the solution continuation depends only on the initial data, so that ATn is independent of N. Hence the series (3.2.41) diverges, which proves the existence and uniqueness of a global classical solution to the auxiliary problem under consideration and, moreover, confirms our assertion that this solution may be constructed by the method of continuation. Moreover, analyticity of u(x,t N) with respect to x for all N > 0 shows that... 

Throughout this chapter, continued reference will be made to the article, Principles of Environmental Analysis , by Keith et al. (I), which should be read by those who request that a method be developed or an analysis be performed. Without elaborating upon the contents, the two most important points of the article are the following (1) It cannot be assumed that the person requesting an analysis will also be able to define the objectives of the analysis properly. (2) Analytical chemists must always emphasize to the public that the single most important characteristic of any result obtained from one or more analytical measurements is an adequate statement of its uncertainty interval (2). ... 

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