Impact of oxcarbazepine sulfate metabolite on incurred sample reanalysis and quantification of oxcarbazepine.

BACKGROUND

Recently, incurred sample reanalysis (ISR) has become a requirement in bioanalysis. The general guidance recommends investigating ISR failure to evaluate the suitability of an analytical method. In the case of acceptable ISR evaluation, there were no precise recommendations for further testing when sporadic values were obtained.

RESULTS

The ISR evaluation performed during a bioequivalence study for the anticonvulsant drug oxcarbazepine showed acceptable ISR results, but one particular chromatographic anomaly led to a thorough investigation. The finding of these tests showed that an oxcarbazepine phase II metabolite occasionally co-eluted with the drug and impacted oxcarbazepine's quantitation through in-source conversion.

CONCLUSION

This paper demonstrates the necessity of rigorous interpretation of ISR results and close monitoring of all subject sample results.