Microdialysis sampling combined with ultra-high-performance liquid chromatography-tandem mass spectrometry for the determination of geniposide in dialysate of joint cavities in adjuvant arthritis rats

Rationale Microdialysis has been used to detect the concentrations of drugs in tissues. Geniposide (GE), an iridoid glycoside compound, is the main bioactive component of Gardenia jasminoides Ellis fruit. We previously demonstrated that GE could control the activity of cytokines and reduce levels of inflammation in adjuvant arthritis (AA) rats, but the topic of concentration changes over time in the joint synovia of AA is scarcely studied. Methods In this study, microdialysis technique combined with ultra-high-performance liquid chromatography-electrospray ionization coupled with tandem mass spectrometry (UHPLC-ESI-MS/MS) was set up and confirmed to assay GE in the dialysate of the joint cavity in AA rats. Mass detection was conducted in multiple reaction monitoring (MRM) mode with negative electro-spray ionization, and Paeoniflorin (Pae) was used as an internal standard (IS). Results A lower limit of quantitation (LLOQ) of 5 ng/mL was found in this method and with good linearity in the range of 5-4000 ng/mL. All the validation data including accuracy, precision, intra and inter-day repeatability and stability meet the requirements. The relative recoveries of GE were determined at approximately 40.01%. Conclusions The measurements based on microdialysis combined with UHPLC-ESI-MS/MS provide a method for sampling and rapid sensitive analysis of GE in dialysate of joint cavity in AA rats. This method should be considered for future pharmacokinetics studies.