Intermediate precision condition

When using replicates, it is required that they are measured at intermediate precision conditions, and not at repeatability conditions. The latter leads to an underestimation of Ecrmcai and consequently most effects will be erroneously considered significant (110). Second, it is recommended to have at least three d.f. available to estimate (SE)e. 

NOTE 2 The specified conditions can be, for example, repeatability conditions of measurement, intermediate precision conditions of measurement, or reproducibility conditions of measurement (see ISO 5725-2 1994). NOTE 3 Measurement precision is used to define measurement repeatability, intermediate measurement precision, and measurement reproducibility. 

Description Measurement precision is usually expressed numerically by measures of imprecision, such as standard deviation, variance, or coefficient of variation, under the specified conditions of measurement. When a measurement precision is given, it is important to specify the conditions. These conditions can be, for example, repeatability condition of measurement, intermediate precision condition of measurement, or reproducibility condition of measurement (see ISO 5725-3 1994 and see below). The measurement precision is used to define measurement repeatability, intermediate measurement precision, and measurement reproducibiUty. In the VIM, it is mentioned that sometimes measurement precision is erroneously used to indicate measurement accuracy. 

Definition Measurement precision under a set of intermediate precision conditions of measurement (Figure 7.3). 

The precision of an analytical procedure expresses the closeness of agreement (degree of scatter) between a series of measurements obtained from multiple sampling of the same homogeneous sample under the prescribed conditions. Precision may be considered at three levels repeatability (within run) intermediate precision (over time) and reproducibility (inter-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. 

Within-laboratory reproducibility/intermediate precision Precision under conditions where independent test results are obtained with the same method on identical test items in the same laboratory by different operators using different equipment on different days. 

Precision and accuracy Quantitative analysis by NMR is very precise with relative standard deviations for independent measurements usually much lower than 5%. The largest errors in NMR measurements are likely due to sample preparation, not the NMR method itself. If a good set of standards is available and all NMR measurements for the test and standard samples are performed under the same acquisition conditions, the quantitative results can be readily reproduced on different instruments operated by different analysts at different times. Therefore, good intermediate precision can also be achieved. An accurate quantitative NMR assay will require accurately prepared standards. The accuracy of an NMR assay can be assessed, for example, by measuring an independently prepared standard or an accurate reference sample with the assay. In many cases, a spike recovery experiment can also be used to demonstrate the accuracy of an NMR assay. 

Precision measures how close data points are to each other for a number of measurements under the same experimental conditions. According to the ICH, precision is made up of three components repeatability, intermediate precision, and reproducibility. The term ruggedness, which has been used in the USP, incorporates intermediate precision, reproducibility, and robustness. 

The intermediate precision is what we encounter in the everyday laboratory practice. A laboratory can, for example, calculate the precision tmder repeatability conditions (same day, same method, same operator etc., but using different equipment, or same equipment but different operators etc.). 

The intermediate derived from attack at the C2 position has greater delocalisation of the positive charge (mesomeric forms 2.28a,b,c) than that derived from attack at the C3 position (mesomeric forms 2.29a,b). As the charge is more extensively delocalised in the former, this intermediate is at lower energy. This in turn is reflected in a lower activation energy for this pathway and manifested in a selectivity for electrophilic substitution at the C2 position over the C3 position. The actual isomer ratio depends on the heterocycle, the electrophile, and the precise conditions, although in many cases such reactions are virtually regiospecific, and only the C2 substitution... 

Although less frequently discussed, heat processes often influence the textures and chemistries of the intermediate and end products, and thermal treatments are not without consequences on milk proteins that are denatured. Denaturation of proteins occurs under precise conditions of pH, temperature and ionic strength leading to their unfolding. Denaturation is significantly slower when proteins are near their isoelectric point. Only (3-lactoglobulin is irreversibly denatured at pH 7 and 70°C a-lactalbumin is denatured at pH 6.7 and 65°C. Aggregation of these proteins, besides hydrophobic... 

The precision has been defined in the ISO 5725-1 standard as the closeness of agreement between independent test results obtained under stipulated conditions [28]. Many factors may contribute to the variability of test results obtained with the same method on identical samples, including (but not limited to) the operators), the equipment, the reagents, the RM(s), the environment, the time between measurements, and the laboratories. The maximal variability of test results is explained by the reproducibility (R) of the method. All factors that have influence on the variability of a test method should be taken into consideration when assessing the reproducibility. The repeatability (r) is assessed by keeping all the above-mentioned factors constant (e.g., same operator, same equipment, same laboratory, short time interval). It is a measure of the minimum variability of a method. The intermediate precision is situated between the two extreme measures of precision repeatability and reproducibility. The terms within-laboratory reproducibility (w), long-term precision, and so on, are often used to demonstrate the intermediate precision of a method. For a correct interpretation of the intermediate precision, the factors that have been taken into account should be known. 

Precision results obtained under some well defined conditions are normally expressed as repeatability, reproducibility or intermediate precision. 

Intermediate precision is the within laboratory variation over a long period of time. The standard deviation will be intermediate in value between that obtained under repeatability and that obtained under reproducibility conditions for similar samples using the same method. 

The precise conditions for the reductive elimination are important. Use of Na(Hg) in THF-MeOH or THF alone gives messy reactions, owing to substantial cleavage of the P—O bond of the enol phosphate but this can be avoided with Na(Hg) in THF-DMSO. Alternatively, Na in liquid ammonia can be used to effect the reductive elimination but the reaction must be very carefully controlled in order to avoid reduction of the alkyne to a tra/ii-alkene. A deliberate over-reduction of the initial alkyne product to an alkene was used in a synthesis of the intermediate (104) in a synthesis of brefeldin (Scheme 35). ... 

Repeatability closeness of agreement between results of successive measurements carried out under the same conditions (i.e., corresponding to within-run precision). Reproducibility closeness of agreement between results of measurements performed under changed conditions of measurements (e.g., time, operators, calibrators, and reagent lots). Two specifications of reproducibility are often used total or between-run precision in the laboratory, often termed intermediate precision and interlaboratory precision (e.g., as observed m external quality assessment schemes [EQAS]) (see Table 14-2). 

Ruggedness. The United States Pharmacopeia (USP) defines ruggedness as the degree of reproducibility of test results obtained by the analysis of the same samples under a variety of normal test conditions, such as different labs, different analysts, different lots of reagents,. Ruggedness is a measure of reproducibility of test results under normal, expected operational conditions from laboratory to laboratory and from analyst to analyst. See Intermediate precision. 

In the regions intermediate between these limiting cases, normal modes of vibration "erode" at different rates and product distributions become sensitive to the precise conditions of the experiment. Intramolecular motions in different product molecules may remain coupled by "long-range forces even as the products are already otherwise quite separated" (Remade Levine, 1996, p. 51). These circumstances make possible a kind of temporal supramolecular chemistry. Its fundamental entities are "mobile structures that exist within certain temporal, energetic and concentration limits." When subjected to perturbations, these systems exhibit restorative behavior, as do traditional molecules, but unlike those molecules there is no single reference state—a single molecular structure, for example—for these systems. What we observe instead is a series of states that recur cyclically. "Crystals have extension because unit cells combine to fill space networks of interaction that define [dissipative structures] fill time in a quite... 

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