Why Are Methods Validated?

This article briefly considers why all analytical methods in chemistry must be validated before they can be used to produce reliable data. Validation of an analytical method is the laboratory process that ensures the method yields accurate and reproducible results. When making analytical measurements, for example, determining the concentration of an illicit drug in a urine sample of an athlete suspected of cheating, it is vital that consistent, reliable and accurate data are reproducibly obtained in a split urine sample (usually labelled A and B) analysed at different times.

This process is important as the test results could lead to the athlete being suspended from competition for several years and the data may well have to stand up to rigorous legal challenge in a court of law. Thus, the objective of validation of an analytical method is to ensure that it achieves its role of reproducible accuracy and is suitable for its intended purpose.

There are many examples of analytical methods that have to be validated and these include:

• Identification of specific chemicals and their concentrations
• Quantitative tests to determine the contents of impurities in different types of samples
• Tests of the active moiety in batches of drugs

Advantages of methods validation

There are a number of very good reasons why analytical methods are validated. First, the laboratory conducting the tests will have an increased output with fewer reductions in rejections of the results. The method is therefore cost effective and avoids additional capital expenditure on other equipment and reduced testing of the finished goods e.g. a batch of drugs.

When should a method be validated?

There are many incidences when a method should be validated. For example, a method needs to be validated if there is a change to the established protocol of an existing method, perhaps because it is thought the new methods will be more cost effective. Any new method developed to solve a particular problem must always be validated.

Furthermore, if an established method is used in different laboratories, which will almost certainly use different equipment and staff, it has to be validated for the accuracy of the results.

Finally, it is important to demonstrate equivalence between any two methods (e.g. a rapid new test versus a long used standard method). Of paramount importance is system suitability testing, which is an integral part of many analytical procedures. In other words, the tests are based on the concept that the equipment, electronics, analytical operations and samples to be analysed constitute an integral reliable and accurate system.

Parameters analysed in methods validation include:

• Specificity – ability to detect a unique chemical unerringly
• Linearity – the method can detect the chemical over an identified linear range
• Accuracy
• Precision
• Detection limit – determines the limit of detection of the chemical of interest
• Quantitation limit – the accuracy of the measurement with suitable statistics
• Robustness – provides an indication of the reliability of the method during normal usage. To read more about robustness, read What is a Robust Method? and Why is my Method Not Robust?  

And Finally, it is important that to note that validation of analytical methods is also required by most regulations and quality standards that impact laboratories in the form of extensive documentation.