Precision repeatability/reproducibility

Performance characteristic A functional quality that can be attributed to an analytical method, for example, specificity, accuracy, trueness, precision, repeatability, reproducibility, recovery, detection capability, and ruggedness. 

Apart from data on precision (repeatability, reproducibility), control charts may be used to check or monitor accuracy, i.e. to what extent the measured value of a quantity (such as the mean particle size, for example) agrees with the accepted value for that quantity, bearing in mind that the true value is never known. In testing accuracy, the standard test powders available on the market may be used. 

Of all the requirements that have to be fulfilled by a manufacturer, starting with responsibilities and reporting relationships, warehousing practices, service contract policies, airhandUng equipment, etc., only a few of those will be touched upon here that directly relate to the analytical laboratory. Key phrases are underlined or are in italics Acceptance Criteria, Accuracy, Baseline, Calibration, Concentration range. Control samples. Data Clean-Up, Deviation, Error propagation. Error recovery. Interference, Linearity, Noise, Numerical artifact. Precision, Recovery, Reliability, Repeatability, Reproducibility, Ruggedness, Selectivity, Specifications, System Suitability, Validation. 

The determination of precision can divided into three categories, namely repeatability, intermediate precision, and reproducibility. Repeatability, or intraassay within-day precision, is determined when the analysis is performed in one laboratory by one analyst, using one definite piece of equipment, and is performed within one working day. Intermediate precision is obtained when the analysis is performed within a single laboratory by different analysts over a number days or weeks, using different equipment, reagents, and columns. Reproducibility represents the... 

Flame AAS can be used to measure about 70 elements, with detection limits (in solution) ranging from several ppm down to a few ppb (and these can be enhanced for some elements by using a flameless source). Both sensitivity and detection limits (as defined fully in Section 13.4) are a function of flame temperature and alignment, etc. The precision of measurements (precision meaning reproducibility between repeat measurements) is of the order of 1-2% for flame AA, although it can be reduced to <0.5% with care. The accuracy is a complicated function of flame condition, calibration procedure, matching of standards to sample, etc. 

The ability to provide accurate and reliable data is central to the role of analytical chemists, not only in areas like the development and manufacture of drugs, food control or drinking water analysis, but also in the field of environmental chemistry, where there is an increasing need for certified laboratories (ISO 9000 standards). The quality of analytical data is a key factor in successfully identifying and monitoring contamination of environmental compartments. In this context, a large collection of methods applied to the routine analysis of prime environmental pollutants has been developed and validated, and adapted in nationally or internationally harmonised protocols (DIN, EPA). Information on method performance generally provides data on specificity, accuracy, precision (repeatability and reproducibility), limit of detection, sensitivity, applicability and practicability, as appropriate. 

Precision is a measure of the ability of the method to generate reproducible results. The precision of a method is evaluated using three separate determinations for repeatability, intermediate precision, and reproducibility. 

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. 

Method precision refers to the variability in measurement of the same sample. There are three main components of method precision repeatability (also known as system or intraassay precision), intermediate precision (also known as inter-assay or intra-laboratory precision), and reproducibility precision (also known as ruggedness, overall or inter-laboratory... 

Precision Repeatability Ruggedness Reproducibility Sample prep replication Injection replication Factorial designs Intra-laboratory study Inter-laboratory study... 

The precision of an analytical procedure expresses the closeness of agreement (degree of scatter) between a series of measurements obtained from multiple samples of the same homogeneous sample under prescribed conditions. Precision is usually investigated at three levels repeatability, intermediate precision, and reproducibility. For simple formulation it is important that precision be determined using authentic homogeneous samples. A justification will be required if a homogeneous sample is not possible and artificially prepared samples or sample solutions are used. 

The more traditional distinction of error components is between random errors and systematic errors. In this classical approach, random errors are generally referred to as precision (repeatability, intermediate precision, and reproducibility), while systematic errors are typically attributed to the uncertainty on the bias estimate and... 

Besides standard deviations and coefficients of variation, repeatability/reproduc-ibility values or limits (r R) are additional parameters of high value in the assessment of precision (see formulas in Table 5). These criteria mean that the absolute variation between two independent results—obtained within the same laboratory respectively between different laboratories—may only exceed the values of r and R in a maximum 5% of the cases [2]. Another measure for the precision is the confidence interval, in which all measurements fall with a certain propability or confidence level 1 - a (a is often 0.05 giving a probability here of 95%) [66]. 

Calculated repeatability, intermediate precision, and reproducibility values can be compared with those of existing methods. If there are no methods with which to compare the precision parameters, theoretical relative reproducibility and repeatability standard deviations can be calculated from the Horwitz equation and the Horrat value (Table 5). Horwitz RSD values are reported in Table 6. Higher variability is expected as the analyte levels approach the detection limit (see below). Next to the Horwitz equation, the AOAC s Peer Verified Program proposes its own levels of acceptability of %RSD as a function of analyte concentration level [56,72]. 

Precision may be considered at three levels repeatability, intermediate precision, and reproducibility (2, 3). Repeatability expresses the precision obtained by repeatedly analyzing, in one laboratory on the same day by one operator using one piece of equipment, aliquots of a homogeneous sample, each of which has been independently prepared according to the method procedure. Repeatability is also termed intra-assay or within-day precision. It is assessed using a minimum of nine determinations. Repeatability can help in determining the sample preparation procedure, the number of replicate samples to be prepared, and the number of injections required for each sample in the final method setting. 

Intermediate precision and reproducibility smdies form much of what historically has been called ruggedness. The variability obtained in the developing laboratory, after considerable experience with the method, is usually less than that achieved by less-experienced laboratories who may later use the method. For this reason, if a method cannot achieve a suitable level of repeatability in the developing laboratory, it cannot be expected to do any better in other laboratories. 

Castro et al. [64] reported a comparison between derivative spectro-photometric and liquid chromatographic methods for the determination of omeprazole in aqueous solutions during stability studies. The first derivative procedure was based on the linear relationship between the omeprazole concentration and the first derivative amplitude at 313 nm. The first derivative spectra were developed between 200 and 400 nm (A/ = 8). This method was validated and compared with the official HPLC method of the USP. It showed good linearity in the range of concentration studied (10—30 /ig/ ml), precision (repeatability and interday reproducibility), recovery, and specificity in stability studies. It also seemed to be 2.59 times more sensitive than the HPLC method. These results allowed to consider this procedure as useful for rapid analysis of omeprazole in stability studies since there was no interference with its decomposition products. 

Accuracy Range Precision Repeatability Intermediate Precision Reproducibility Precision System Precision Method Specificity Selectivity Linearity... 

The ICH has broadened and redefined these terms to more accurately describe the method s ability to reproducibly generate analytical results. Precision is defined as a combination of repeatability, intermediate precision, and reproducibility. Repeatability is system precision, as defined previously. Intermediate precision includes multiple analyses by multiple analysts on different days using different equipment within a given laboratory. This is only the first step in demonstrating the ruggedness of the method. 

Precision should be measured using a minimum of five determinations per concentration. A minimum of three concentrations in the range of expected concentrations is recommended. The precision determined at each concentration level should not exceed 15 % of the coefficient of variation (CV) except for the LLOQ, where it should not exceed 20 % of the CV. Precision is further subdivided into within-run, intrabatch precision or repeatability, which assesses precision during a single analytical run, and between-run, interbatch precision or reproducibility, which measures precision with time, and may involve different analysts, equipment, reagents, and laboratories. Since it is not always easy to obtain data about the reproducibility in the strict sense it often makes sense to use intermediate precision this expresses within-laboratories variations on different days, by different analysts, and on different equipment, etc. [60],... 

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. 

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