Method precision sample repeatability

Rodriguez-Otero et al. (46) tried to measure cheese composition by NIR in cheese. They tried to analyze cheese without any prior sample manipulation (not even grating) on the basis of increased knowledge in calibration techniques based on multivariate analysis. Repeatability of NIR moisture determination was approximately double in comparison with the reference method. Repeatability of determination of protein by reference (Kjeldahl) and NIR methods was higher for the NIR spectroscopy, probably because of the large sample size rather than to a lack of method precision. The repeatability of fat determination by reference (gravimetric extraction) and NIR methods was 0.31% for reference and 0.40% for NIRS. 

Precision The repeatability characterizes the degree of short-term control exerted over the analytical method. Reproducibility is similar, but includes all the factors that influence the degree of control under routine and long-term conditions. A well-designed standard operating procedure permits one to repeat the sampling, sample work-up, and measurement process and repeatedly obtain very similar results. As discussed in Sections 1.1.3 and 1.1.4, the... 

Analysis precision, n - a statistical measure of the expected repeatability of results for an unchanging sample, produced by an analytical method or instrument for samples whose spectra represent an interpolation of a multivariate calibration. The reader is cautioned to refer to specific definitions for precision and repeatability based on the context of use. 

The precision of a test method is the variability between test results obtained on the same material using a specific test method (ASTM, 2004 Patnaik, 2004). The precision of a test is usually unrelated to its accuracy. The results may be precise, but not necessarily accurate. In fact, the precision of an analytical method is the amount of scatter in the results obtained from multiple analyses of a homogeneous sample. To be meaningful, the precision study must be performed using the exact sample and standard preparation procedures that will be used in the final method. Precision is expressed as repeatability and reproducibility. 

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... 

Validation of methods for quantitative determination of impurities includes precision studies. Repeatability is generally assessed by analysis of the same sample or samples prepared by the same analyst in replicate assays within a short duration of time. Repeatability should be assessed using (i) a minimum of nine determinations covering the specified range for the procedure (e.g., three concentrations/three replicates each) or (ii) a minimum of six determinations at 100% of the test concentration. Repeatability is evaluated by averaging the mean results from replicate assays and calculating the standard deviation (SD) and RSD. Repeatability of the method can be stated as either SD or RSD values. If an instrument is required for assay performance, then the same instrument should be used for the replicate assays. 

Automated methods are more reliable and much more precise than the average manual method dependence on the technique of the individual technologist is eliminated The relative precision, or repeatability, measured by the consistency of the results of repeated analyses performed on the same sample, ranges between 1% and 5% on automated analyzers. The accuracy of an assay, defined as the closeness of the result or of the mean of replicate measurements to the true or expected value (4), is also of importance in clinical medicine. 

In addition to analytical and nonanalytical repeats, some samples in certain studies need to be reassayed to demonstrate incurred sample reproducibility (ISR). This type of testing is a critical step for demonstrating the reproducibility of the bioanalytical method with samples from dosed subjects (as distinct from precision demonstrated with QCs, i.e., blank matrix spiked with drug). Written procedures in this regard should include a description of how the samples are selected for reanalysis, the comparison and reporting of the original and repeat results, and the acceptance criteria for variability between results. 

The precision of an analytical method is obtained from multiple analyses of a homogeneous sample. You can determine overall precision of the method, including sample preparation. Such precision data are obtained by one laboratory on one day, using aliquots of the homogeneous sample that have been independently prepared. Such interlaboratory precision is called repeatability. Interlaboratory precision, if appropriate, is also determined as part of a measurement of reproducibility or robustness of the method (see below). 

Precision-. The USP defines precision as the degree of agreement among individual test results when the method is applied repeatedly to multiple samplings of a homogeneous sample. Precision may be measured as repeatability, reproducibility, and intermediate precision. 

The attractive features of splitless injection techniques are that they allow the analysis of dilute samples without preconcentration (trace analysis) and the analysis of dirty samples, since the injector is easily dismantled for cleaning. Success with individual samples, however, depends on the selection of experimental variables of which the most important sample size, sample solvent, syringe position, sampling time, initial column temperature, injection temperature and carrier gas flow rate, often must be optimized by trial and error. These conditions, once established, are not necessarily transferable to another splitless injector of a different design. Also, the absolute accuracy of retention times in splitless injection is generally less than that found for split injection. For splitless injection the reproducibility of retention times depends not only on chromatographic interactions but also on the reproducibility of the sampling period and the evaporation time of the solvent in the column inlet, if solvent effects (section 3.5.6.2) are employed. The choice of solvent, volume injected and the constancy of thermal zones will all influence retention time precision beyond those for split injection. For quantitative analysis the precision of repeated sample injections is normally acceptable but the method is subject to numerous systematic errors that may... 

The least-squares procedure just described is an example of a univariate calibration procedure because only one response is used per sample. The proccs.s of relating tiiulliple instrument responses to an analyte or a mixture of analytes is known as multivariate calihnt-lion. Multivariate calibration methods have become quite popular in recent years as new- instruments become available that produce multidimensional responses (absorbance of several samples at multiple wavelengths, mass spectrum of chroniaiographically separated components, etc.). Multivariate calibration methods are very powerful. They can he used to simultaneously determine multiple components in mixtures and can provide redundancy in measurements to im-proNc precision because repeating a measurement N limes provides a vN improvement in the precision of ilie menu value (see. Appendix I.. Sccli< n al IM). They can also be u.scd to delect the presence of interferences that would not he ideniilied in a univariate calibration. 

RSD of 2% or less for a HPLC assay method for a small molecule drug product or API. For impurity measurements, the %RSD will increase as the spiked level decreases. Typical acceptance criteria at 0.1% levels are 10-25% RSDs, whereas at a 1% level, %RSD criteria are set at 3-5%. An example of accuracy and precision results obtained from a recovery study for Degradation Product A from XYZ Tablets by one analyst is presented in Table 8.2. Another method for measuring repeatability is to analyze a homogenous sample multiple times, for example 6 x samples at 100% of test concentration and then determine the %RSD. 

Precision of a chemometric method refers to the reproducibility of the method. For quantitative chemometric methods, it is important to test both the instrument and method precision. Instrument precision is done by repeating measurements on the same sample method precision is the closeness of replicate sample measurements while intermediate precision can be evaluated by running the same samples with different analysts on different days. 

Precision - integration, particularly at low sample amounts, may be difficult and an assessment of the precision of the experiment is needed. As alluded to above there are three levels of precision testing repeatability, intermediate precision and reproducibility. Repeatability expresses the precision under the same operating conditions over a short interval of time. This is frequently the only precision information provided in literature reports. Intermediate precision expresses within-laboratory variations across different days, different analysts, different equipment, etc. and it is a key indicator of how an assay will perform under real conditions. Reproducibility expresses the precision between laboratories and typically only becomes important if a method is transferred between laboratories - for example, from an R D site to a manufacturing facility. 

Bioanalytical method validation guidelines recommend using a minimum of three samples at low, mid, and high concentrations across the calibration curve range for precision testing. Measurements should include the evaluation of precision or repeatability within a single analytical run... 

Validation A test of the overall analytical method to establish that it meets pre-specified performance criteria, including analyte identity, LOD and LLOQ, dynamic range and linear dynamic range, accuracy, reproducibility (within-day precision) and repeatability (between-day precision), selectivity (freedom from interferences), sample stability under various relevant conditions etc. 

The precision of a gas chromatographic method is the measure of agreement or closeness of analyte concentrations to each other when the analyses were performed using identical conditions, i.e. the same method, same sample, same operator, and same laboratory conditions over a short period of time. This is known as repeatability. This is generally the measure of the amount of scatter in the results obtained from multiple analyses of a sample. Mathematically it is calculated and expressed as standard deviation (SD). 

The precision of repeatability was determined by three analysts preparing six samples each on a single day. The intermediate precision was determined by the same analysts with six samples each on six different days. The method accuracy was determined with 0.04 mg/kg. 

What is the precision of the measurement method Precision refers to the statistical variability among repeated measurements of the same sample. Often, especially when trace levels of chemicals are measured, the statistical variability of the measurements may be on the order of plus or minus several tens of percent, even when properly done by a qualified laboratory. (Of course, much worse precision may be expected from careless lab work.) A good analytical chemist always quantifies the precision of the measurement method by conducting multiple analyses of selected samples and standards. 

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