Simultaneous determination of duloxetine and 4-hydroxy duloxetine glucuronide in human plasma and back-conversion study

Aim: To develop an LC-MS/MS method for simultaneous determination of duloxetine and its metabolite, 4-hydroxy duloxetine glucuronide (4HDG) in human plasma and to investigate the potential back-conversion of 4HDG to duloxetine using stability study. Materials & methods: The LC-MS/MS method was validated according to the EMA and USFDA Bioanalytical Method Validation Guidelines and applied to pilot bioequivalence study. Results & conclusion: The method validation results were within the acceptance limits. The stability study and incurred sample reanalysis results ruled out the occurrence of back-conversion. The study highlighted the conduct of back-conversion test and the advantages of LC-MS/MS method in terms of sensitivity, specificity and low consumption of organic solvents.

Automated summary

The study successfully developed an LC-MS/MS method for simultaneous determination of duloxetine and its metabolite 4HDG in human plasma, with results meeting validation guidelines. The study highlighted the advantages of using LC-MS/MS method in bioequivalence studies, and ruled out the back-conversion of 4HDG to duloxetine.