Acceptable precision

Numerous examples of standard methods have been presented and discussed in the preceding six chapters. What we have yet to consider, however, is what constitutes a standard method. In this chapter we consider how a standard method is developed, including optimizing the experimental procedure, verifying that the method produces acceptable precision and accuracy in the hands of a single analyst, and validating the method for general use. 

Quality assurance programs are designed to serve two functions (1) assessment of collected air quality data and (2) improvement of the data collection process. These two functions form a loop as air quality data are collected, procedures are implemented to determine whether the data are of acceptable precision and accuracy. If they are not, increased quality control procedures are implemented to improve the data collection process. 

This reaction has been regarded by previous authors as the prototype of o reactions (2, 28). It also figured heavily in the definition of the a" parameters of Wepster for —R para substituents (2e). However, we find that the data set for this reaction series is not fitted with acceptable precision by eq. (1) and data fitted even as well by other parameters (for Oi (BA)> SD=. 43, f=. 329 for S L parameters, SD=. 38, /=. 287). Thus, the data for this set appear truly exceptional. The largest deviations for individual substituents in the fitting with cr (A) parameters are found among both -R (NMe2, NH2, F) and +R (NO2 and MeCO) substituents. Because the data sets for both m- and p- substituents meet the minimal basis set requirements, we have utilized these in a manner similar to that described for the definition of Ur(a) parameters to obtain a comparative set of parameters. 

Eq. (1) has potential application to other types of measurements of substituent effects besides those specifically considered in this paper e.g., nmr coupling constants and shifts for other nuclei, ir and uv spectral shifts and intensities. We caution (with emphasis) in these applications the needed use of data sets of high quality, both with respect to the precision of the measurement and substituents considered (i.e., a full complement of substituent o/ and Or properties must be encompassed for a meaningful correlation to be obtained). There is, of course, no requirement that all data sets will be uniquely fitted by eq. (1) using one of the four or scales of Table V. For example, the data for the ionization of the conjugate acids of pyridine-N-oxides (30), HjO, 25° is found to fit equally well the or(ba.) or Or scales (SD=. 14 /=. 072). The data (31) for the rates of alkaline ("OMe) cleavage of ArSnMea are not fitted to acceptable precision (fs >. 23) by any of the Or parameters. This data set is nevertheless indicated... 

No properly constituted data sets for reaction rates were found for which eq. (1) is followed with acceptable precision (34). This result may be attributed to the incursion of proximity effect contributions. However, certain benzoic acid type ionization equilibria data sets do appear to follow eq. (1) satisfactorily, although none of the sets qualifies as a minimal basis set. Table XXVII summarizes the results for the fittings with parameters, which for every discriminating... 

Decay of the nuclide itself. The conceptually simplest approach is to take a known quantity of the nuclide of interest, P, and repeatedly measure it over a sufficiently long period. The observed decrease in activity with time provides the half-life to an acceptable precision and it was this technique that was originally used to establish the concept of half-lives (Rutherford 1900). Most early attempts to assess half lives, such as that for " Th depicted on the front cover of this volume, followed this method (Rutherford and Soddy 1903). This approach may use measurement of either the activity of P, or the number of atoms of P, although the former is more commonly used. Care must be taken that the nuclide is sufficiently pure so that, for instance, no parent of P is admixed allowing continued production of P during the experiment. The technique is obviously limited to those nuclides with sufficiently short half-lives that decay can readily be measured in a realistic timeframe. In practice, the longest-lived isotopes which can be assessed in this way have half-lives of a few decades (e.g., °Pb Merritt et al. 1957). 

In a traditional, two-way cross-over study, blood samples are taken at predetermined times (e.g., 0.5, 1, 1.5, 3, 6, 9, 12, 24, and 36 hours after dosing). The samples are assayed for drug (and if necessary metabolites). Fortunately, analytical methods, especially HPLC, are now available that make the quantification of many drugs in blood or serum convenient, rapid, and relatively inexpensive. The method selected should normally have an acceptance precision so that concentrations of drug of one tenth Cmax can be reliably quantified. 

The CL system luminol-hydrogen peroxide was characterized by Hoshino and Hinze in HTAC reversed micelles, formed in a 6 5 (v/v) chloroform-cyclohexane mixture [63], The results indicate that such a CL system can be used from an analytical point of view in a pH interval of 7.8-9.0 without the need to add a catalyst or a co-oxidant. In these conditions an analytical method was established for determination of hydrogen peroxide that, apart from supplying much milder conditions compared to the usual situation in an aqueous medium, is also acceptably precise and reproducible. 

For high-throughput analysis, it is important to increase the specihcity of each bioanalytical method. The enhancement of chromatographic resolution presents various limitations. Better selectivity can be obtained with TOF mass analyzers that routinely provide more than 5000 resolution (full width at half-mass or FWHM). The enhanced selectivity of a TOF MS is very attractive for problems such as matrix suppression and metabolite interference. In one report of quantitative analysis using SRM, TOF appeared less sensitive than triple quadrupole methods but exhibited comparable dynamic range with acceptable precision and accuracy.102... 

On comparison with known Koppel-Pahn equation the equation (1) includes square of Hildebrandt s solubility parameter 2 [5], P.219-225. This equation (1) allows with acceptable precision degree to generalize all data from the work [1] (see Table) without necessity of exclusion the data for ethylacetate ... 

The energetic charactiristics of process such as E ACt AH, AG and AS also can be generalized with acceptable precision by means of five parameters equations. As an example in the table there are given the experimental activation energies (E ACt) and its values calculated by equation (3) ... 

With respect to the torsion constants of these 43- and 69-bp restriction fragments, the fitting procedure was not robust, and acceptable precision could not be attained. 

Fig. 13.1 Reduced vapor pressure and molar density vs. reciprocal reduced temperature for HoO, CH4, H2, and 4He. In each case, were simple corresponding states theory adequate, all data would lie on a single master curve. Using extended CS the curves are fit to acceptable precision, (a) (top) = reduced vapor pressures, (b) (bottom) = reduced liquid molar densities... 

Figure 13.1a shows reduced vapor pressures and Fig. 13.1b reduced liquid molar densities for the parent isotopomers of the reference compounds. Such data can be fit to acceptable precision with an extended four parameter CS model, for example using a modified Van der Waals equation. In each case the parameters are defined in terms of the three critical properties plus one system specific parameter (e.g. Pitzer acentric factor). Were simple corresponding states theory adequate, the data for all... 

Finally, we will discuss the determination of the limit of quantitation or LOQ. Establishing an LOQ is required for many pharmaceutical applications such as impurity testing and cleaning validation. Limit of quantitation is the lowest concentration (%, ppm) that can be determined with acceptable precision (RSD of —5%). It is generally accepted that a signal/noise ratio at the LOQ should be at least There are... 

Quantitation limit is the lowest concentration of analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions. 

Precision studies can be planned in a full factorial matrix-type format involving multiple analysts, days, capillaries, buffer preparations, instruments, etc. Table 9 displays an example matrix for intermediate precision testing involving two analysts, two instruments, and two capillaries over a multiple day period. Typically, qualification targets for acceptable precision will be pre-defined based on method type, capability, and intent. Acceptable targets can also be mathematically determined by the method of Horwitz. ... 

When v > 1 the equation equivalent to equation 15 is of order higher than quadratic, a cubic when v = 2 and a quartic when v = 3. The solution of these equations, though possible, does not lead to a value of X of acceptable precision. 

However, even against this background of uncertainty and apparent imprecision, in some cases it is possible to measure airborne asbestos with acceptable precision through replication for a reasonable price. Since there is no exposure standard, "clean" must be defined by comparing indoor and outdoor levels. A statistical comparison of indoor versus outdoor measurements that is significantly different from zero indicates that the indoor space is not clean. Tests may be designed chat either compare the average of... 

Because of the potential legal consequences on the suspect(s) and the subjects involved, forensic analyses require high quality standards and have to be subjected to extensive quality assurance and rigid quality control programs. For example, the enforcement of laws establishing a sanction based on the presence/concentration of a substance in blood (e.g., cocaine in a driver s blood) requires that the substance is correctly identified and reliably determined with acceptable precision and accuracy. 

Time of death is almost invariably among the requests that detectives ask to forensic scientists. Nonetheless, this is a very difficult question to answer, at least with an acceptable precision. 

The main prerequisite for the quantification of low-molecular weight compounds by MALDl MS is the use of internal standards and optimized analysis protocols. For example, the quantification of alanine using 1- C-alanine as labeled internal standard in the system [C4CiIm][PFg]/CCA was possible with acceptable precision [14]. The method is therefore suited for screening processes, for example, for the comparison of enzyme activities in ILs. The detectability of peptides and proteins itself in this context also allows for an... 

Acceptance criteria for precision depend very much on the type of analysis. For pharmaceutical quality control, precision of better than 1 % RSD is easily attained, while for biological samples the precision is more like 16% at the detection limit and 10% at higher concentration levels. For environmental and food samples, the precision is very much dependent on the sample matrix, the level of the analyte, and on the analytical method, being in the range of 2% to more than 20% RSD. Acceptable precision values as a function of the analyte concentration have been suggested (11) by the Association of Official Analytical Chemists (AOAC) peer-verified methods program (Table 25.1). 

The working range of an analytical method is the interval between the upper and lower concentrations of the analyte in the sample for which it has been demonstrated that the method has acceptable precision, accuracy and linearity. This interval is normally derived from linearity studies and depends on the intended application of the method. However, validating over a range wider than actually needed provides confidence that the routine standard levels are well removed from nonlinear response concentrations, and allows quantitation of crude samples in support of process development. The range is normally expressed in the same units as the test results obtained by the analytical method. 

At least lOmg of water must be present in the sample to obtain an acceptable precision, given the magnitude of the equivalent water titre T of the commercial reagent needed. When the amount of water is lower than this (as low as 10 pg of water), the coulometric method must be used to increase sensitivity. 

This technique has been applied to data from a set of 42 samples from a nuclear detonation. Samples were taken both from fallout collectors and from airborne-debris samplers. Twenty-seven radionuclides could be identified and measured with acceptable precision (better than 10% ) in at least some of the samples. The results are presented in Table I. This calculation was performed without the added variance term Fik. The nuclides include both fission and activation products. 

Our results indicated that coals ground to —60 mesh failed to yield a consistently acceptable precision for most trace element determinations. Therefore, it was necessary to evaluate the errors associated with trace element determinations in coals ground to various particle sizes. 

Modified filter sampling methods that are available will measure ambient levels of strong acid in ambient aerosol samples, and these methods do so with acceptable precision and accuracy [as indicated by the balance between measured anions and cations (56, 57)] in the absence of significant levels of particulate weak acids. Additional intercomparisons involving intrinsically different techniques for particulate strong acidity [e.g., IR spectroscopy (48), thermal speciation (38, 45), and filter methods (28)] are needed. Further information on the occurrence of various weak acids in airborne particles is needed, along with further studies of techniques for their specific determination in atmospheric aerosol samples. 

The standard deviation (SD) of all the results from their group means was 0.07 mg/C. The SD from the results of duplicate assays on urine samples was 0.12 mg/f in the 1-10 mg/f range (30 samples with a mean pregnanediol concentration of 3.88 mg// ). This data implies that pregnanediol concentrations in urine of below 0.2 mg/C cannot be analyzed with acceptable precision by this method. 

Unfortunately it is not easy to assess what parameters play the greatest role in maintaining acceptable precision and accuracy. One must consider the assumptions inherent in the theory as well as the chemical, mechanical, and instrumental parameters. Generally, gas chromatographic methods agree within 1-5% of other methods. The speed and simplicity of the gas chromatographic method continue to make it very attractive for physicochemical measurements. 

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