Accuracy, Precision and Limit of Detection

In terms of characterizing, the ultimate performance of PTR-MS as a measurement technique, it is useful to quantify the accuracy and precision of any quantitative determination. The reader is reminded of the definitions of these two terms accuracy reveals how close a series of measurements are to the true value of the desired quantity, while precision is a measure of how reproducible each consecutive measurement is. Thus if multiple measurements of a trace gas concentration are made under identical conditions, the best estimate of the concentration will be the mean of these values. However, there is no guarantee that the mean value will be close to the true value, since systematic errors may be incorporated in this determination. As an example, if the rate coefficient used in the application of Equation 4.1 differs from the true value by a factor of two, then this relatively large error will be incorporated into the determination of the gas concentration. All of the potential sources of error for concentration determinations discussed in Section 4.4 are sources of systematic error. 

For a Poisson distribution, the degree of random scatter in the measured count rate is reflected in the standard deviation, a, which is given by 

For reasonable data acquisition times of a few seconds, the best attainable LODs via PTR-MS are on the order of a few tens of pptv, with significant variations from compound to compound [10], 

---

Many of these methods suffer from interferences and limited sensitivity and they can be labor intensive and difficult to automate. Although performance criteria (accuracy, precision, and limit of detection) can be specified for analytical methods, it is still difficult to obtain similar results in different laboratories. For example, there are over 200 available methods to assay for... 

A 5 pm GraceSmart C18 column (250 mm x 4.6 mm i.d.) was used for the iso-cratic separation of these drugs with an eluent consisting of 38 62 (v/v) formic acid in water/acetonitrile. Among the tested additives, 0.1% formic acid yielded the best peak shapes. The analysis of the four antidiabetic drugs could be conducted in less than 8 min. In their study, Jia et al. [155] also compared charged aerosol detection with UV and ELSD in order to evaluate performance parameters such as linearity, accuracy, precision, and limit of detection. As a result. 

This chapter deals with issues encountered when using PTR-MS as a quantitative technique. It starts by showing how the concentration of a gas constituent can be calculated from a PTR-MS measurement without calibration, and then moves on to consider why calibration can be important. The most commonly used methods for trace gas calibration are then described. The chapter closes with a discussion of the accuracy, precision and limit of detection for PTR-MS measurements. 

An analytical method vahdation study should include demonstration of the accuracy, precision, specificity, limits of detection and quantitation, linearity, range, and interferences. Additionally, peak resolution, peak tailing, and analyte recovery are important, especially in the case of chromatographic methods (37,38). 

A number of experimental considerations must be addressed in order to use XRF as a quantitative tool, and these have been discussed at length [75,76]. The effects on the usual analytical performance parameters (accuracy, precision, linearity, limits of detection and quantitation, and ruggedness) associated with instrument are usually minimal. 

Method validation is the process of proving that an analytical method is acceptable for its intended purpose.3 In pharmaceutical chemistry, method validation requirements for regulatory submission include studies of method specificity, linearity, accuracy, precision, range, limit of detection, limit of quantitation, and robustness. 

The United States Pharmacopoeia (U.S.P.) [5] in a chapter on validation of compendial methods, defines analytical performance parameters (accuracy, precision, specificity, limit of detection, limit of quantitation, linearity and range, ruggedness, and robustness) that are to be used for validating analytical methods. A proposed United States Pharmacopeia (U.S.P.) general chapter on near-infrared spectrophotometry [6] addresses the suitability of instrumentation for use in a particular method through a discussion of operational qualifications and performance verifications. 

This section defines the basic concepts used in this chapter (e.g., calibration, accuracy, precision, hnearity, limit of detection, and others). 

The most important parameters in method validation for bioanalysis applications are linearity, precision, accuracy, selectivity, and limits of detection and quantification. In... 

Accuracy and precision Specificity Limit of detection Limit of quantitation Linearity and range... 

The reliability of multispecies analysis has to be validated according to the usual criteria selectivity, accuracy (trueness) and precision, confidence and prediction intervals and, calculated from these, multivariate critical values and limits of detection. In multivariate calibration collinearities of variables caused by correlated concentrations in calibration samples should be avoided. Therefore, the composition of the calibration mixtures should not be varied randomly but by principles of experimental design (Deming and Morgan [1993] Morgan [1991]). 

For a method to be considered as part of commercial specification, validation using ICH guidelines (Q2A and Q2B) is required (see also Chapters 9 and 10). Depending on method characteristics, different validation schemes may be used. The following parameters should be considered to ensure the method is valid and appropriate for its intended purpose accuracy, precision (repeatability, intermediate precision), specificity, limit of detection (LOD), limit of quantification (LOQ), linearity, and range. 

Tire performance of an analytical method and its inherent reliability are characterized by a set of quality parameters that determine its applicability and its usefulness, b or a quantitative method, the most notable parameters are its precision, accuracy, and limit of detection. For a qualitative method, the most important characteristic is its reliability in the identification of the analyte. Since there may be found in the literature an enormous set of different methods for analyzing a particular analyte in a particular matrix, it must be decided which method is the most appropriate for the analysis. 

CONTENTS 1. Chemometrics and the Analytical Process. 2. Precision and Accuracy. 3. Evaluation of Precision and Accuracy. Comparison of Two Procedures. 4. Evaluation of Sources of Variation in Data. Analysis of Variance. 5. Calibration. 6. Reliability and Drift. 7. Sensitivity and Limit of Detection. 8. Selectivity and Specificity. 9. Information. 10. Costs. 11. The Time Constant. 12. Signals and Data. 13. Regression Methods. 14. Correlation Methods. 15. Signal Processing. 16. Response Surfaces and Models. 17. Exploration of Response Surfaces. 18. Optimization of Analytical Chemical Methods. 19. Optimization of Chromatographic Methods. 20. The Multivariate Approach. 21. Principal Components and Factor Analysis. 22. Clustering Techniques. 23. Supervised Pattern Recognition. 24. Decisions in the Analytical Laboratory. 

In 1990, the USP 22 guideline listed eight individual parameters that must be investigated and documented in order to validate a method 1) Accuracy 2) precision 3) limit of detection 4) limit of quantification 5) selectivity 6) range 7) linearity and 8) ruggedness. 

There is a general agreement that at least the following validation parameters should be evaluated for quantitative procedures selectivity, calibration model (linearity), stability, accuracy (bias, precision) and limit of quantification. Additional parameters which might have to be evaluated include limit of detection, recovery, reproducibility and ruggedness (robustness) [2,4-10,12],... 

If TLC is used as an analytical method in quality control, the reproducibUity, i.e. lack of scatter (precision of both system and method), and also the accuracy of the analytical results must be determined. The GMP/GLP guidelines also require vahdation of the method, i.e. testing for linearity, selectivity, robustness and limits of detection and determination (see also Section 9.1 Validation of TLC Methods ). For method development, high demands are placed on the stationary phases of the chromatographic system ... 

The solid state NMR is applicable for soluble, insoluble structural analysis of chitin/chitosan samples it can be used for entire range of the DA determination no need to prepare and to dry the sample some information on chemical structure, sequence of co-monomer units and type of copolymers (random and block) can be obtained from the spectra of chitin/ chitosan samples the more sensitive instrument generally results in the higher precision resolution, limit of detection and accuracy of results are improved using cross polarization and strong magnetic fields. 

The objective of this chapter will be to propose a scheme for demonstrating the accuracy, precision, and suitability of sensors. As will be seen, no matter what sensor, device, or measurement approach is chosen, these three simple criteria will be at the heart of the calibration/validation exercise. Depending on the complexity of the process, the sensor system, and process requirements necessary to achieve a mechanistic understanding, more parameters may be necessary. For example, linearity, range, specificity, robustness, raggedness, detection limit, and quantification hmit may also need to be investigated. By definition (see calibration and validation definition in this chapter), accuracy, precision, and suitability will be the minimum requirements for the cahbration/validation exercise of process sensors. 

QC material should be prepared in drug-free plasma containing the same anticoagulant as the samples to be tested. In addition, it is advisable to assess the sensitivity and limit of detection with different matrices using your own LC-MS/MS system. This may differ between matrices and have consequences for the precision and accuracy of detection of the assay. 

---