Low-volume plasma sampling for determination of dextromethorphan and dextrorphan in rat plasma: LC-MS/MS method and its application in pharmacokinetic study

Dextromethorphan (DM) and its metabolite dextrorphan (DX) continue to draw the attention of researchers owing to their diverse pharmacodynamics. Thus, there are possibilities for repurposing DM. Most of the pharmacodynamics of DM needs further validation in different preclinical models. Also, it is necessary to correlate the pharmacodynamics with relevant pharmacokinetics data. Multiple bioanalytical techniques developed for this purpose primarily use a high sample processing volume. Since sample volume is a limiting factor for many preclinical models, an effort was taken to develop an alternative method suitable for handling low sample processing volumes. An efficient solid-phase extraction technique, robust liquid chromatographic (LC) separation and highly sensitive tandem mass spectrometric detection (MS/MS) showed suitability for use of a 30 mu l sample processing volume. This led to the development of a highly specific, selective, accurate and precise-bio-analytical method for simultaneous quantification of DM and DX in rat plasma. The validated method was linear in the range of 0.196-403.356 ng/ml for DM and 0.102-209.017 ng/ml for DX. The application of the method was demonstrated through the estimation of pharmacokinetic parameters that showed good congruence with earlier studies.

Automated summary

Dextromethorphan (DM) and its metabolite dextrorphan (DX) have diverse pharmacodynamics, but further validation in different preclinical models and correlation with relevant pharmacokinetics data is needed. A new method using solid-phase extraction, liquid chromatographic separation, and mass spectrometric detection was developed for low sample volumes. This method allowed for the simultaneous quantification of DM and DX in rat plasma and yielded accurate pharmacokinetic parameters.