Variations in internal standard response: some thoughts and real-life cases

Internal standards are essential to ensure the reliability of chromatographic bioanalytical methods. However, this only holds true if the response of the internal standard is adequately monitored. A difference needs to be made between isolated variations in a limited number of samples, which can be easily handled using objective criteria triggering the re-analysis of the affected samples and more complex situations such as trends or systematic differences, which may require the use of scientific judgment, trigger further investigations and ultimately result in the rejection of analytical runs.