Relative standard deviation validation

Few populations, however, meet the conditions for a true binomial distribution. Real populations normally contain more than two types of particles, with the analyte present at several levels of concentration. Nevertheless, many well-mixed populations, in which the population s composition is homogeneous on the scale at which we sample, approximate binomial sampling statistics. Under these conditions the following relationship between the mass of a randomly collected grab sample, m, and the percent relative standard deviation for sampling, R, is often valid. ... 

A system suitability test prescribes a relative standard deviation of not more than 1% for the procedure to be valid with Xmean = 173.5 this translates into Vr - (1.735)2 because the limit is imposed, this is equivalent to having no uncertainty about the numerical value, or in other words,/r = Since Si was determined to be 2.43 for n, = 1 ... 

Option (Valid) presents a graph of relative standard deviation (c.o.v.) versus concentration, with the relative residuals superimposed. This gives a clear overview of the performance to be expected from a linear calibration Signal = A + B Concentration, both in terms of (relative) precision and of accuracy, because only a well-behaved analytical method will show most of the residuals to be inside a narrow trumpet -like curve this trumpet is wide at low concentrations and should narrow down to c.o.v. = 5% and rel. CL = 10%, or thereabouts, at medium to high concentrations. Residuals that are not randomly distributed about the horizontal axis point either to the presence of outliers, nonlinearity, or errors in the preparation of standards. 

The CE method was validated in terms of accuracy, precision, linearity, range, limit of detection, limit of quantitation, specificity, system suitability, and robustness. Improved reproducibility of the CZE method was obtained using area normalization to determine the purity and levels of potential impurities and degradation products of IB-367 drug substance. The internal standard compensated mainly for injection variability. Through the use of the internal standard, selected for its close mobility to IB-367, the method achieved reproducibility in relative migration time of 0.13% relative standard deviation (RSD), and relative peak area of 2.75% RSD. 

This 2D-method was validated for the concentration range between 0.005 and 0.5 pmol for D-amino acids and 0.05-5 pmol for L-amino acids. Within-day and interday precisions were always better than 8% relative standard deviation (RSD) and the accuracies for spiked rat plasma samples were between 95.5% and 100.2%. Limit of detections (LCDs) and limit of quantitations (LOQs) were reported to be as low as 3 fmol (S/N = 3-5 corresponding to 0.15 nmolg wet tissue) and 5 fmol (corresponding to 0.25 nmolg wet tissue). It was concluded that this assay is supposed to be one of the most sensitive analysis method for amino acid enantiomers in mammalian samples. 

Cleaning validation 6 replicates at 10 x LOQ Relative standard deviation NMT 20%... 

Coppola [329] suggested that phenolic acid prohle could be used as an indicator of apple juice adulteration. Shui and Leong [330] reported the simultaneons determination in apple juice on an ODS column with methanol/snlfnric acid/water as the mobile phase within 80min. However, (-)-epicatechin and p-conmaric acid may be elnted with a similar retention time, so that the spectrum must be recorded in order to identify single compounds. The method was validated and intraday and interday relative standard deviation (RSD%) data resnlted within 0.3% and 1.6%, respectively. The paper also reports LOD data that range between 0.03 mg/L (syringic acid) and 0.18 mg/L (benzoic acid). 

FIGURE 9 Hierarchy of, relationship between, and objectives and requirements for prevalidation [106], validation [62,63, 68], and standardization of analytical methods [62, 63, 67, 68,75,84] RSD = relative standard deviation, CV = coefficient of variation, SOP = standard operating procedure. 

The results of these interlaboratory studies are reported in USEPA Method Validation Studies 14 through 24 (14). The data were reduced to four statistical relationships related to the overall study 1, multilaboratory mean recovery for each sample 2, accuracy expressed as relative error or bias 3, multilaboratory standard deviation of the spike recovery for each sample and 4, multilaboratory relative standard deviation. In addition, single-analyst standard deviation and relative standard deviation were calculated. 

Quality assurance wasn t satisfied with just having the data meet all the specifications or have a relative standard deviation below 6%. It was not confident that tablets in the batch with lower potency would be adequate to allow the normal expiration date for the product. Quality assurance thus did not agree that the process in the new area should be approved (i.e., validate, especially when data from the earlier blending process indicated a more uniform product. 

The absorption of pantoprazole at 295 nm was used for the quantitative determination, and the method validated and used for the analysis of pantoprazole in its tablets. The results of validation study indicated that the method is linear over the range of 1.0 to 3.0 mg/mL (r= 0.9999). The percent recovery and relative standard deviation were 99.3-101.5 (n=9), and less than 1.0%, respectively. This method can be used for quality control and routine analysis [5],... 

The resulting metal, in the salt state, is dissolved in nitric acid and diluted to a known volume with double distilled water. The solution is analyzed by Atomic Absorption for the metals of interest. Metals such as Cadmium, Berylium and Nickel have very low threshold limit values which are set by OSHA and are frequently present in the sample in very low quantities. Many Atomic Absorption units are equipped with a hollow graphite tube atomizer which increases the sensitivity dramatically making it easier for the analyst to obtain reliable results for species present in the sample in very low concentrations. The validity of the metal fume data depends on sampling train calibration and the precision and accuracy of the analytical procedure. NIOSH has reported a 2% relative standard deviation in the analytical method which has been collaboratively tested. 

Determination Determine the precision of an analytical method by assaying a sufficient number of aliquots of a homogeneous sample to be able to calculate statistically valid estimates of standard deviation or relative standard deviation (coefficient of variation). Assays in this context are independent analyses of samples that have... 

Prior to performing a formal validation, the analytical chemist should have performed some prevalidation during method development. The expectation is that a well-developed HPLC method should subsequently be validated with no major surprises or failures. Prior to validation, specificity and some degree of robustness should be demonstrated. In addition, some form of system suitability criteria will have been established. System suitability evaluates the capability of an HPLC system to perform a specific procedure on a given day. It is a quality check to ensure that the system functions as expected and that the generated data will be reliable. Only if the system passes this test should the analyst proceed to perform the specific analysis. System suitability can be based on resolution of two specified components, relative standard deviation, tailing factor, limit of quantitation or detection, expected retention times, number of theoretical plates, or a reference check. 

Figure 16-3. Bergum acceptance curve for evaluating content uniformity (CU) data. Note The curve shows that for a relative standard deviation (%RSD) of 4.5%, a sample mean value (SMV) of 100% must be achieved for the manufacturing process to be judged as validated.

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