Quantification of remifentanil and propofol in human plasma: a LC-MS/MS assay validated according to the EMA guideline

Background: Remifentanil and propofol are often used in combination for general anesthesia. We developed a method using LC–MS for their simultaneous measurement in human plasma. Methodology & results: After addition of remifentanil-13C6 and propofol-d18 (IS), 500 µl of plasma were extracted with ethylacetate/hexane. Analysis conditions included gradient elution (water/acetonitrile), electrospray ionization and detection with a triple quadripole mass spectrometer. Remifentanil and propofol were ionized in the positive and negative mode, respectively. The method was validated according to the European Medicines Agency guideline for the validation of bioanalytical methods, then successfully applied to clinical samples from three patients who had undergone liver transplantation. Conclusion: This method is suitable for the simultaneous quantification of remifentanil and propofol in clinical studies.