Abstract
Internal standard (IS) response has been an active topic of discussion within the bioanalytical community. Initial discussions focused on developing criteria for anomalous responses. Recently, understanding the cause and potential impact of variable IS response has been emphasized. Following a review of recommendations from industry discussions regarding variable IS responses, case studies where interferences with IS response resulted in quantitation inaccuracy are presented. The examples illustrate that variable IS response cannot always be attributed to compensation of matrix effects. Anomalous IS responses, even for stable label internal standards should be investigated and the root cause for the anomalous behavior should, if possible, be determined.
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