Standard deviation within-batch

Content uniformity is a USP test is designed to establish the homogeneity of a batch. Ten tablets are assayed individually after which the arithmetic mean and relative standard deviation (RSD) are calculated. USP criteria are met if the content uniformity lies within 85-115% of the label claim and the RSD is not greater than 6%. Provision is included in the compendium for additional testing if one or more units fail to meet the standards. 

Workers at the Department of the Environment UK [174] have described continuous flow methods for the determination of total oxidised nitrogen and nitrite in seawater. limits of detection are 1.3 pg/1 (total oxidised nitrogen) and 0.26 pg/1 (nitrite). Within-batch standard deviations for total oxidised nitrogen range from 0.28 pg/1 to 17.5 pg/1 at the total oxidised nitrogen level, to 0.96 pg/1 at the 560 pg/1 total oxidised nitrogen level. Within-batch standard deviations for nitrite range from 0.056 pg/1 at the 3.5 pg/1 nitrite level to 0.042 pg/1 at the 70 pg/1 nitrite level. 

A control sample is a sample for which the concentrations of the test analyte is known and which is treated in an identical manner to the test samples. It should ideally be of a similar overall composition to the test samples in order to show similar physical and analytical features. For instance, if serum samples are being analysed for their glucose content, the control sample should also be serum with a known concentration of glucose. A control sample will be one of many aliquots of a larger sample, stored under suitable conditions and for which the between batch mean and standard deviation of many replicates have been determined. It may be prepared within the laboratory or purchased from an external supplier. Although values are often stated for commercially available control samples, it is essential that the mean and standard deviation are determined from replicate analyses within each particular laboratory. 

We are starting with the case where we have a control sample that covers the whole analytical process inclnding all sample preparation steps. The matrix of the control sample is similar to that of the routine samples. Then the standard deviation of the analysis of this sample (under between-batch conditions) can be used directly as an estimate for the reproducibility within the laboratory. The standard deviation can be taken directly from a control chart for this control sample (see chapterl3). In the table two examples are shown for different concentration levels. 

In our laboratory, control values that fall within 2 standard deviations of the mean are considered acceptable and require no further action. Any control values that are either greater than 2 standard deviations or trends require review by a laboratory director. The laboratory director decides whether the analysis of the complete batch or of specific samples needs to be repeated and initiates troubleshooting. 

As internal control for sterol analysis in plasma, serum, and liquor, each series of samples includes a 150 pi aliquot of a large batch of control plasma samples in which cholestanol and cholesterol concentrations are determined and compared with previously determined concentrations. The values for these should fall within 2 standard deviations. The control plasma sample is composed of pooled plasma samples of different individuals stored as 150-pi aliquots at - 18°C. 

Mean drying time for the oven tray process is 19.2 hr. All 15 batches were dried within the specified time of 16 to 20 hr. No seasonal influence was apparent. The average moisture content of these batches is 1.2% the standard deviation is 0.3%. The 15 batches dried using the fluid bed dryer had a residual moisture of 0.8% (SD = 0.1%). Drying time is mechanically controlled and not recorded. The statistics favor the fluid bed process it is more efficient and uniform. There is nothing in these data to disqualify the oven tray dryer from further use, however. 

Most of the indices of the mixing capacity in the left-hand side column in Table 2.1 are related to the mixing rate—residence time for the flow system (e.g., ratio of the standard deviation of the probability density distribution of the residence time to the average residence time residence time is the stay time of the inner substance in an equipment), circulation time for a batch system (e.g., ratio of the standard deviation of the probability density distribution of the circulation time to the average circulation time circulation time is the time required for one circulation of the inner substance in an equipment), mixing time (e.g., the time required for the concentration of the inner substances at a specific position in the equipment to reach a final constant value within some permissible deviation), and so on. 

Recendy, rapid separation of enantiomers by CEC had been carried out in less than 1 min [86], and the high reproducibility of the separation was consistent in over 30 runs. Batch-to-batch reproducibility was reported to be within 5% relative standard deviation as measured by the migration time of an unretained solute using nine different monolithic columns, and run-to-run reproducibility of within 1% relative standard deviation [87]. 

Reproducibility during column preparation is a significant problem in CEC. Preparation methods involving pumped slurries were all found to produce generally highly efficient (> 200,000 plates/m for 3-pm ODS particles), but within a batch of columns packed by the same method, the relative standard deviation (RSD) of EOF, and migration time and retention factor of a standard were [23], respectively, 7-14%, 5-22%, and 9-30%. These values are particularly relevant to considerations of the transfer of HPLC methods to CEC. 

This procedure has been repeated in our laboratory and in production (modified version) hundreds of times, and the average for 1993 activity/acid-base ratio was 96%, with a standard deviation of 2%. This indicates that, if the proper procedure is followed, then a reproducible yield of Grignard reagent can be attained. The most common variation on this preparation is the type of Mg activation (see Chapter 4). Other recommended preparations can be found within this book (see especially Chapters 3 and 4) and in the literature [continuous process Ref. 41 and batch process Refs. 42, 43]. 

LOQ) will typically be higher than the instrumental detection limit (IDL), because of background analyte and matrix-based interferences. The BEC (blank equivalent concentration) used in Table 4.7 is the apparent concentration of an analyte normally derived from intercepted point of its calibration curve or by reference of the actual counts for that analyte in a blank solution. The BEC gives a good indication of the blank level, which will affect the IDL. Most often, the detection limits are calculated as three times the normal standard deviation of the BEC in a within batch replicate analytical measurement of a blank solution. Therefore, if the instrument is stable enough, this will give a better IDL than the BEC itself. The BEC is a combination of the contamination of the analyte in the solution, the residual amount of the analyte in the spectrometer and the contribution of any polyatomic species in the analyte mass. 

Precision, which quantifies the variation between replicated measurements on test portions from the same sample material, is also an important consideration in determining when a residue in a sample should be considered to exceed a MRL or other regulatory action limit. Precision of a method is usually expressed in terms of the within-laboratory variation (repeatability) and the between-laboratory variability (reproducibility) when the method has been subjected to a multi-laboratory trial. For a single-laboratory method validation, precision should be determined from experiments conducted on different days, using a minimum of six different tissue pools, different reagent batches, preferably different equipment, and so on, and preferably by different analysts Repeatability of results when determined within a single laboratory but based on results from multiple analysts is termed intermediate precision Precision of a method is usually expressed as the standard deviation. Another useful term is relative standard deviation, or coefficient of variation (the standard deviation divided by the absolute value of the arithmetic mean result, multiplied by 100 and expressed as a percentage). 

In addition to the validation of the analytical method, routine methods should include several controls to ensure the quality of the reported data [32,37]. The most usual approach consists of the injection of blank samples spiked at the LOQ and 10 x LOQ levels, that is, quality controls (QC), in each batch of samples analyzed. For quality control compliance, a QC recovery range of 60—140% is used in routine multiresidue analysis [32]. Recoveries outside this range would require reanalysis of the sample batch. Results for samples that exceed MRL residue levels must be supported by individual recovery results in the same batch within the range of the mean recovery (70—120%) 2 RSD (relative standard deviation), at least for the confirmatory analyses. 

Results for each batch are deemed acceptable when results for the control sample fall within the average percent carbon residue three standard deviations. Control results, which are outside these limits, indicate problems with the procedure or the equipment. 

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