Determining Accuracy

Develop final Perform structural design of analysis of component acceptable accuracy Determine structural response—stresses, support reactions, deflections, and stability—based on a structural analysis of acceptable accuracy. Determine acceptable accuracy based on economic value of component, consequences of failure, state-of-the-art capability in stress and stability analysis, margin of safety, knowledge about loads and materials properties, conservatism of loads, provisions for further evaluation by prototype testing... 

Add an aliquot of the hydrazine-modified protein solution to the p-nitrobenzaldehyde solution and incubate at 37°C for 1 hour or at room temperature for 2 hours. To assure accuracy, determine the linear response range of the test by adding a series of different concentrations of the hydrazine-modified protein solution to the p-nitrobenzaldehyde buffer. This is done by preparing a set of serial dilutions of the protein solution and... 

Proposed reference Selected metal temperature [mK] Observed Tc and Wc [mK] Accuracy determination of Tc... 

Sampling accuracy Determine gravimetrically the average volume of water withdrawn from a tared vial filled with water after six 50- lL injections 50 2pL... 

Instead of using spike samples (as in accuracy determination), drug product lots that are representative of the commercial products should be used for precision (repeatability, intermediate precision). This is to ensure that the commercial drug product is used in at least one part of the method validation and that the repeatability results are representative of those that can be expected in the future. 

Typically, linearity and accuracy determination covers a wide concentration range (e.g., 50% of the ICH reporting limit to 150% of specification). However, the concentration range for precision will be limited by the availability of sample of different related substance levels. Therefore, to ensure an appropriate method validation range with respect to precision, it is critical to use samples of low and high levels of related substance in precision experiments (e.g., fresh and stressed samples). 

Accuracy. Sample solutions of known concentration (e.g., spiked placebo) are used for the accuracy determination. Experimental work may be organized so that the same stock solutions are used to prepare both linearity and accuracy solutions. The accuracy solution must be exposed to normal test conditions (e.g., mixing in a heated dissolution vessel). Determine any bias that is caused by the sampling and analysis of the solutions. If a dissolution profile of the drug product is required, accuracy determinations at different concentrations of the required profile will need to be performed (e.g., at 40, 75, and 110% of theoretical release). The results are reported as percent theory. 

Accuracy determines the closeness of the analytical data to the true value. It is estimated from the recovery of a known standard spiked into the sample. Based on the percent spike recovery, a correction for the bias may be made. Routine environmental analyses generally do not require such corrections in the results. However in specific types of analysis, correction for bias may be required when the percent spike recovery for a QC batch sample is greater than 0 and less than 100. In the wastewater analyses for certain organics, U S. EPA has set forth the range for percent recovery. If the spike recovery for any analyte falls outside the range, the QC criteria for that analyte is not met. 

TABLE 5.2 Accuracy Determined by Relative Difference and Bias... 

To establish reasonable acceptance criteria for accuracy during planning, we should obtain statistical laboratory control limits from the laboratory that will perform analysis for the project samples. We should also be aware of matrix interferences in environmental samples that may reduce the accuracy of analysis. As part of QC procedures, to estimate the effects of matrix interference on accuracy, laboratories perform the accuracy determinations on environmental samples, known as matrix spike (MS) and matrix spike duplicate (MSD). These fortified samples enable the laboratory to detect the presence of interferences in the analyzed matrices and to estimate their effect on the accuracy of sample analysis. (In the absence of matrix interferences, an additional benefit from MS/MSD analysis is an extra measure of analytical precision calculated as the RPD between the two recoveries.)... 

Moore LJ, Machlan LA (1972) High accuracy determination of calcium in blood serum by isotope dilution mass spectrometry. Anal Chem 44 2291-2296... 

Use of the thermochemistry discussed above allows rough estimation of reaction enthalpy for a wide range of reactions involving resonance-stabilized radicals. Furthermore, reaction entropies and heat capacities may often be estimated to a good level of accuracy (+ 1-2 cal/mol K) (7b). Hence, equilibrium constants may be estimated to a level of accuracy determined primarily by the uncertainty in reaction enthalpy. 

K. von Klitzing, G. Dorda, and M. Pepper, M. (1980). New method for high-accuracy determination of the fine-structure constant based on quantized Hall resistance, Phys. Rev. Lett. 45 494 97 (1980). 

While steel samples may be used as reasonable, alternatives to iron meteorites in accuracy determinations they would not be as suitable in comparisons with silicate rocks. A granite Gl and a diabase W1 have been suggested as international standards for the determination of the major and minor constituents of igneous rocks. A number of workers using several separate methods including neutron activation have determined the... 

Comparing the leading order term in (15.75) with the step value in (15.74), we see that the inverse formula provides the correct estimate of a step, b, with the accuracy determined by the leading term in the representation (15.75). However, Bleistein inversion is based on a Born approximation formula which is valid only to leading-order in 6cg. Thus the theoretical inversion result for this simple model fits well the basic assumption of the Bleistein method. 

Stokes, P. O Connor, G. Development of a liquid chromatography-mass spectrometry method for the high-accuracy determination of creatinine in serum. J. Chromatogr., B 2003, 794, 125-136. 

There are only a few studies dealing with method validation of the determination of environmental pollutants by CE. However, some authors have demonstrated the application of their developed separation methods. The accuracy determination for Na, K, Ca, and Mg metal ions has been presented. Similarly, the precision of migration times and peak areas for seven alkali and alkaline earth metals has been measured RSD values were less than 0.4% for migration times and from 0.8% to 1.8% for peak areas.In one of the experiments, the reported %RSD varied from 2.79 to 3.38 for Zn, Cu, and Fe metal ions. Several other studies have shown reliable results with recoveries close to 100%, or good agreement with the results obtained by other methods.In spite of this, the precision of linearity, sensitivity, and reproducibility of CE methods for metal ions and anions analysis are not better than ion chromatography. 

Procedural guidelines for accuracy determination include replicate analysis, e.g., three to six assays, at five levels, over the range from 80% of the lowest expected assay value to 120% of the highest expected assay value, or from 75% to 125% of label claim, six samples of drug in the matrix spanning 50% to 150% of the expected content. At minimum, three concentrations must be used within the analytical range (extremes and midpoint of expected or near quantitation limit, center of range, and upper bound of standard curve). 

Problem 8.29 The problem of reproducibility of rates and the discrepancy between results obtained by various authors is usually attributed to variations in impurity levels, the most important being the traces of water. To determine the minimum concentration levels at which water can still be effective, consider a polymerization where [M] = 0.1 mol/L, ki = 3 L/mol-s and the of the polymer formed is 10 (these values are reasonably close to a styrene polymerization) and assume that a rate of 1% conversion per 24 h can be determined with sufficient accuracy. Determine the concentration of water in the system containing a Lewis acid (L) coim tiator in a relatively large concentration. 

It is interesting to mention that the statistical inefficiency is obtained only after performing the simulation and therefore it is of little practical use until the simulation is halted. However, for our applications in solvent effects it shows that within a given accuracy determined only by the total number of MC steps there is a great saving of the total calculation if only uncorrelated structures are used in the subsequent quantum mechanical calculations. For the case of the acetone-water calculations only 40 uncorrelated structures are used for the ensemble average of the calculated quantum mechanical results, instead of the total number of 32000. 

Therefore, the values of pEMe0 determined by averaging the titration data from the initial section of the titration curve (characterized by a sharp e.m.f. reduction at small titrant additions) are just the dissociation constant of the studied oxide, to an accuracy determined by the natural spread of the experimental data. It should be emphasized, however, that the values of the pEMeQ concentration constant calculated in such a way, contain an appreciable error, caused by the fact that the initial concentration of the titrant in the halide melt is comparable in magnitude with that of oxygen-containing admixtures in the pure melt. 

---