Systematic errors internal standards

The precision stated in Table 10 is given by the standard deviations obtained from a statistical analysis of the experimental data of one run and of a number of runs. These parameters give an indication of the internal consistency of the data of one run of measurements and of the reproducibility between runs. The systematic error is far more difficult to discern and to evaluate, which causes an uncertainty in the resulting values. Such an estimate of systematic errors or uncertainties can be obtained if the measuring method can also be applied under circumstances where a more exact or a true value of the property to be determined is known from other sources. 

Accuracy (systematic error or bias) expresses the closeness of the measured value to the true or actual value. Accuracy is usually expressed as the percentage recovery of added analyte. Acceptable average analyte recovery for determinative procedures is 80-110% for a tolerance of > 100 p-g kg and 60-110% is acceptable for a tolerance of < 100 p-g kg Correction factors are not allowed. Methods utilizing internal standards may have lower analyte absolute recovery values. Internal standard suitability needs to be verified by showing that the extraction efficiencies and response factors of the internal standard are similar to those of the analyte over the entire concentration range. The analyst should be aware that in residue analysis the recovery of the fortified marker residue from the control matrix might not be similar to the recovery from an incurred marker residue. 

There is no consistent trend with fraction neutralization, so the correlating equation is adequate. However, series 3 is high and series 8 is low, suggesting systematic errors. Each of series 2 through 8 are internally consistent, with standard deviations around a mean error less than 17%. 

Accuracy is the closeness of agreement between what is accepted as a true value (house standard, international standard) and the value found (mean value) after several replicates. This also provides an indication of systematic error. 

After the transfer of the specimen and the addition of internal standard, the drug-to-internal ratio becomes a fixed quantity. Any additional random or systematic volume errors should not affect the concentration estimate. Upon injection of the reconstituted extract onto the HPLC, however, random errors will occur that do affect the estimate. These are the result of chance deviations in the partitioning of the drug... 

The systematic errors introduced by flow rate differences may be avoided by adding to the solutions a minimum amount of a low-molecular-weight internal standard (o-dichloro benzene, toluene, acetone, sulfur) which must not interfere with the polymer peaks. Flow rate is monitored in each chromatogram by measuring the retention time of the internal standard, and eventual variations may be corrected accordingly. 

The accuracy of a method is affected by systematic (bias) as well as random (precision) error components [3, 9] This fact has been taken into account in the definition of accuracy as established by the International Organization for Standardization (ISO) [17]. However, it must be mentioned that accuracy is often used to describe only the systematic error component, i.e. in the sense of bias [1, 2, 6-8,10,12, 13]. In the following, the term accuracy will be used in the sense of bias, which will be indicated in brackets. 

The internal standard method can compensate for several types of errors that can be caused by sample matrix. Systematic errors due to matrix effects can sometimes be avoided. The internal standard method can also correct for fluctuations in experimental conditions amount of sample analysed, sample introduction, emission source temperature assuming that the signal analyte and internal standard are influenced to the same extent. The main advantage of the internal method over usual calibration methods is that it can provide excellent accuracy and precision and at the same time correct for variable viscosity affects. The method is limited by the availability of a suitable reference element that behaves almost as close to the analyte under test in terms of ionisation energy, solubility, low memory effects, etc. 

Water can be determined in solid samples by infrared spectroscopy. The water content of calcium sulfate hydrates is to be measured using calcium carbonate as an internal standard to compensate for some systematic errors in the procedure. A series of standard solutions containing calcium sulfate dihydrate and a constant known amount of the internal standard are prepared. The solution of unknown water content is also prepared with the same amount of internal standard. The absorbance of the dihydrate is measured at one wavelength ( sample) along with that of the internal standard at another wavelength (As,d). The following results were obtained. 

External quality assurance (EQA) is fundamental to the standardization of clinical laboratory methods because it provides a means to compare results generated in one laboratory with those of peer laboratories subscribing to the same EQA program. EQA programs are especially beneficial since internal QA and QC procedures are limited in their ability to detect bias in analytical methods. Internal QA/QC can only detect errors that result in a deviation from the original method validation inherent errors in the method may go unnoticed. Therefore, it is helpful to compare the results produced by a new method with those from other laboratories (Burtis and Ashwood, 2001). Monitoring the performance of laboratory procedures in a consistent manner keeps the laboratory accountable, and can reveal systematic errors that would otherwise be undetected. A prominent component of EQA is proficiency testing. 

These standard errors are purely internal to the calculation in that they are correct only when consistent systematic errors are absent from the data. The values would... 

It can be assumed that with the development and study of new methods, the ability to determine M (S), the method bias component of uncertainty, cannot be done given that it can be evaluated only relative to a true measure of analyte concentration. This can be achieved by analysis of a certified reference material, which is usually uncommon, or by comparison to a well-characterized/accepted method, which is unlikely to exist for veterinary drug residues of recent interest. Given that method bias is typically corrected using matrix-matched calibration standards, internal standard or recovery spikes, it is considered that the use of these approaches provides correction for the systematic component of method bias. The random error would be considered part of the interlaboratory derived components of uncertainty. 

Internal standards are useful for correcting systematic errors that occur in some assays, but the need for one should be identified before spending time and effort on finding one. 

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