Quality control matrix effects

False-positive results with bDNA have been observed with proficiency testing specimens for HTV-1 in the College of American Pathologists HIV-1 viral load survey and HCV in the viral quality control program administered by the Netherlands Red Cross. The reason for the false-positive results with these proficiency testing specimens is not known but may be sample matrix effects. The extent to which this problem occurs with clinical samples has not been determined. However, both the HIV-1 and HCV bDNA assays were designed to have a false-positive rate of 5%. 

The results described here demonstrate the importance of appropriate treatment and monitoring in actual drinking water processing plants, with attention to the specific requirements of the raw water matrix in use. In particular, the adverse effect of certain processes, namely pre-chlorination, which has been implicated in the inhibition of biodegradation in subsequent steps, and in the formation of alternative metabolites, is highlighted. Furthermore, the variable efficiency of GAC filtration in practice, emphasises the need for regular monitoring and quality control. The duration of specific process steps has also been shown to influence the efficacy of the technique, and should be addressed in application. 

The strict regulations of the pharmaceutical industry have a significant effect on the quality control of final products, demanding the use of reliable and fast analytical methods. The capacity that the technique has for the simultaneous determination of several APIs with no need of, or with minimum, sample preparation has considerably increased its application in pharmaceutical analytical control. The main limitation of NIR is the relatively low sensitivity that limits the determination of APIs in preparations when their concentration is less than 0.1%. Nevertheless, instrumental improvements allow the determination below this limit depending on the nature of the analyte and the matrix, with comparable errors to the ones obtained with other instrumental techniques. The reference list presents an ample variety of analytical methodologies, types of samples, nature of analyte and calibration models. A detailed treatment of each one is beyond the scope of... 

A minimum of 2 ml EDTA blood is placed immediately on ice and centrifuged within 30 min at 2000 xg for 5 min at 4°C. Plasma is immediately deproteinised by adding 1 ml to 0.625 ml of 10% 4 and mixing thoroughly by vortex. The mixture is frozen and stored at -70°C until analysis. 1-ml aliquots of pooled plasma collected from healthy subjects are prepared and stored in the same way and are used to prepare AdoMet and AdoHcy calibration standards to allow for matrix effects and also as an internal quality control. CSF is collected in plain tubes and kept at -70°C until analysis. 

A selective, sensitive, and rapid hydrophilic interaction liquid chromatography with electrospray ionization tandem mass spectrometry was developed for the determination of donepezil in human plasma [32], Donepezil was twice extracted from human plasma using methyl-ferf-butyl ether at basic pH. The analytes were separated on an Atlantis HILIC Silica column with the mobile phase of acetonitrile ammonium formate (50 mM, pH 4.0) (85 15, v/v) and detected by tandem mass spectrometry in the selective reaction monitoring mode. The calibration curve was linear (r = 0.9994) over the concentration range of 0.10-50.0 ng/ ml and the lower limit of quantification was 0.1 ng/ml using 200 /d plasma sample. The CV and relative error for intra- and inter-assay at four quality control levels were 2.7% to 10.5% and —10.0% to 0.0%, respectively. There was no matrix effect for donepezil and cisapride. The present method was successfully applied to the pharmacokinetic study of donepezil after oral dose of donepezil hydrochloride (10 mg tablet) to male healthy volunteers. 

Due to the differences between spiked samples (calibration standards and quality controls) and incurred samples as well as the potential inter sample differences, variations in internal standard response during incurred sample analysis are somewhat expected and they should be monitored with predetermined criteria to identify any potential bioanalysis abnormality. Many different factors (not necessarily only matrix effect) could cause variations in internal standard responses during incurred sample analysis. The same phenomenon, e.g., consistently higher IS responses for all the samples of a subject, can be caused by different reasons. Accordingly, each case should be dealt with individually with an open mind. 

Several recommendations arose from the interlaboratory smdy to minimize analytical challenges and to ensure data quality. As discussed above, it is recommended that mass labelled PFCs be employed as internal standards [93, 97]. It should be noted, however, that some electrospray ionization suppression may still occur if these internal standards are used at high concentrations [97]. Matrix effects can also be minimized by employing matrix-matched calibration standards in lieu of solvent-based calibration standards [97]. Unfortunately, matrix-matched standards can be impractical when an appropriate clean matrix cannot be found [94]. Other quality assurance and quality control measures, such as spike and recovery analyses of an analyte added to the sample matrix, repetitive analysis of samples to determine precision and comparison of internal standard quantitation to quantitation via standard additions, are also useful in determining data quality [94]. 

As mentioned earlier, the matrix-related random interferences may not be independent. In this case, simple addition of the components is not correct, because a covariance term should be included. However, we can estimate the combined effect corresponding to the bracket term, which then strictly refers to the CV of the differences (CV b2-rb])- As in the case with constant standard deviations, information on the analytical components is usually available, either from duplicate sets of measurements or from quality control data, and the combined random bias term in the second bracket can then be derived by subtracting the analytical component from CV21. Systematic and random errors can then be determined, and it can be decided whether a new field method can replace an existing one. Figure 14-31 shows an example with proportional random errors around the regression line. 

C4. Clark, P. M. S., Whitehead, T. P., and Kricka, L. J., Application of analytical isotachophoresis in the study of the protein matrix of quality control sera and the effects of lyophilisatlon. Proc. ITP 80. Elsevier, Amsterdam, 1981. 

For quality control reasons, rapid screening methods are needed to identify the volatiles in polymeric materials collected for recycling. HS-SPME-GC-MS was shown to be a fast and sensitive method to screen for brominated flame retardants in recycled polyamide materials [78]. HS-SPME effectively extracted several brominated compounds, all possible degradation products from the common flame-retardant Tetrabromobisphenol A from recycled polyamide 6.6. Furthermore, the high extraction capacity of the PDMS/DVB stationary phase towards aromatic compounds was demonstrated, as the HS-SPME-GC-MS method allowed the extraction and iden-tiflcation of brominated benzenes, from a complex matrix only containing trace amounts of analytes. In addition, degradation products from an antioxidant, a hindered phenol, were extracted. Figure 14 shows a typical chro-... 

HS-SPME is a very useful tool in polymer analysis and can be applied for absolute and semi-quantitative determination of the volatile content in polymers, for degradation studies, in the assessment of polymer durabihty, for screening tests and for quality control of recycled materials. For quantitative determination of volatiles in polymers, SPME can be combined with multiple headspace extraction to remove the matrix effects. If the hnearity of the MHS-SPME plot has been verified, the number of extractions can be reduced to two, which considerably reduces the total analysis time. Advantages of MHS-SPME compared to MAE are its higher sensitivity, the small sample amount required, solvent free nature and if an autosampler is used a low demand of labor time. In addition, if the matrix effects are absent, the recovery will always be 100%. This is valuable compared to other techniques for extracting volatiles in polymers in which the recovery should be calculated from the extraction of spiked samples, which are very difficult to produce in the case of polymeric materials. 

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