Methods of validating a test instrument
FDA regulations such as GMP, GLP and GCP and quality standards such as ISO17025 require analytical methods to be validated before and during routine use.
Analytical method validation is the process used to authenticate that the analytical procedure employed for a specific test is suitable for its intended use.
For assay methods, spiked samples are prepared in triplicate at three levels over a range of 50-150% of the target concentration.
After extraction of the analyte from the matrix, its recovery can be determined by comparing the response of the extract with the response of the reference material dissolved in a pure solvent.
The parameters, as defined by the ICH and by other organizations and authors, are described in brief in the following paragraphs.
The term specificity usually refers to a method that produces a response for a single analyte only, while the term selectivity refers to a method that provides responses for a number of chemical entities that may or may not be distinguished from each other.
The objective of reproducibility is to verify that the method will provide the same results in different laboratories (collaborative studies, usually applied to standardization of methodology) with different analysts, and by using operational and environmental conditions that may differ from, but are still within, the specified parameters of the method (inter laboratory tests).
The acceptance criteria for precision depend very much on the type of analysis.
The precision of a method can be subdivided into 3 categories: repeatability, intermediate precision and reproducibility.Repeatability is obtained when the analysis is carried out in a laboratory by an operator using a piece of equipment over a relatively short time span.Intermediate precision is determined by comparing the results of a method run within a single laboratory variations: different days, different analyst, different equipment, etc.Since there are very few methods that respond to only one analyte, the term selectivity is usually more appropriate.The USP defines the selectivity of an analytical method as its ability to determine an analyte accurately in the presence of interference, such as synthetic precursors, excipients, enantiomers and known (or likely) degradation products that may be expected to be present in the sample matrix.
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Pharmaceutical QC precision of greater than 1percent RSD is easily achieved for compound analysis, but the precision for biological samples is more like 15 percent at the concentration limits and 10 percent at other concentration levels dependent on the sample matrix, the concentration of the analyte, the performance of the equipment and the analysis technique.