Instrumentation, testing, and data validation

FIGURE 8-1 Example of impedance measurement setup with a frequency-response analyzer and a four-electrode cell 

In the present state-of-the-art equipment it is possible to measure and plot the electrochemical impedance automatically. The generator can be programmed to sweep from a maximum to a minimum frequency in a number of required frequency steps. Thus the measurement frequency is changed automatically, and the total measurement time for one experiment can be predetermined. For example, for a measurement using five samples per every decade of frequency, it takes 31 seconds to take a sweep from 50 kHz to 0.1 Hz, 5 minutes 30 seconds for a sweep from 50 kHz to 0.01 Hz, and almost 54 minutes for a sweep from 50 kHz to 0.001 Hz. Automatic plotting of the experimental data can be performed by computer software in different graphical representa- 

Single-sine equipment—lock-in amplifier and frequency-response analyzer 

If a reference signal (typically a square waveform) is a voltage of frequency (0 according to  

The mean level of which is the DC component of the detector signal, 

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Extraction scientist who is responsible for sample preparation should be certified prior to extracting real study samples. The validated extraction method has to be followed exactly. The raw data entries have to be documented promptly such as lot numbers of STD and QC, IS, extraction reagents, matrix, the IDs of automation tool and pipette, the time for study sample removal and return to storage and the completion of extraction. Instrument operator who is responsible for analysis has to perform SST test and assess sensitivity and carryover prior to initialing batch. Instrument operator has to... 

The validation process determines the amount of error owing to variation among the values in the population. It is used to check for the existence of a relationship between the calibration set and the validation set. Manufacturers of NIRS instrumentation include software packages that allow the operator to predict analytical results on data files that have been stored, thus allowing for validation of the calibration equation and testing for errors in the developed calibration. This enables calibration equation performance testing in terms of precision. The validity of these models depends on the ability of the calibration set to accurately represent the samples in the prediction set. 

Usually, the linearity of a NIR spectroscopic method is determined from the multiple correlation coefficient (R) of the NIR predicted values of either the calibration or validation set with respect to the HPLC reference values. It may be argued that this is an insufficient proof of linearity since linearity (in this example) is not an independent test of instrument signal response to the concentration of the analyte. The analyst is comparing information from two separate instrumental methods, and thus simple linearity correlation of NIR data through regression versus some primary method is largely inappropriate without other supporting statistics. 

The quality of the end result fundamentally depends on the sample, the data, the measurement process, the transformation of data to information and, finally, the display and transformation of the information. It is obvious that the role of the instrument in providing the integrity of data is also fundamental to the end result. Written requirements for instrumental performance are not sufficient for assuring the reliability of the result unless they are tested and validated. 

It may be appropriate to mention here various criticisms concerning the validity of the analysis of the experimental data [Blostein 2001 Blostein 2003 (b) Cowley 2003], However, the results of a considerable number of instrumental and experimental tests, as well as related Monte Carlo simulations, have demonstrated the excellent working conditions of Vesuvio and the validity of the data analysis procedure, thus refuting the aforementioned criticisms for an account in detail, see Ref. [Mayers 2004] and the additional experimental tests presented in the next section. 

Thus, if quality is established in terms of precision and reproducibility of the results obtained in the studies (i.e. in the respective sets of measurements or experiments), the need to provide for each of the studies a study plan, approved by the head of the laboratory before the experiments or measurements can be started, will not be an important consideration. Certainly, Standard Operating Procedures will have to be observed, and the acknowledged methods will have to be followed, with any deviations to be described and justified. Since it is the quality of the result which counts for the determination of the test facility s quality , and not the way on which it has been obtained, there is no need for a single point of study control in the person of the Study Director. Certainly, a laboratory head will have to be appointed, who has to ensure that the quality of the data obtained in the laboratory remains high, and who has to provide the necessary education and training for the technical personnel in order to enhance and update their technical expertise. If precision and reproducibility are the primary purpose of the test facility s quality concerns, then apparatus, instruments, equipment and computerised systems have to comply to the highest technical standards in terms of validation, maintenance and calibration. 

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