Online microdialysis-ultra performance liquid chromatography-mass spectrometry method for comparative pharmacokinetic investigation on iridoids from Gardenia jasminoides Ellis in rats with different progressions of type 2 diabetic complications.

Iridoid glycosides consist the main bioactive constituents of Gardenia jasminoides Ellis (G. jasminoides), which is used alone or in combination with other medicine herbs for treatment of diabetes mellitus in China. This paper investigated for the first time comparative pharmacokinetics (PKs) of four unbound iridoids (including genipin, geniposide, gardenoside and geniposidic acid) in rat blood between healthy and type 2 diabetic groups with different disease progressions (9 or 13 weeks). Online microdialysis-ultra performance liquid chromatography-mass spectrometry (MD- UPLC-MS/MS) method was used after oral administration of iridoid extracts obtained from the fruits of G. jasminoides. Student's t-test was used for statistical comparison of PK parameters. Results showed that genipin, geniposide and geniposidic acid feature higher Cmax , larger area under the curve (AUC), lower clearance (CL), longer Tmax and mean residence time (MRT) in type 2 diabetic rats than those in healthy rats (p<0.05). However, no significant difference was observed in PK parameters between the two diabetic groups with different complication progressions (p>0.05). Type 2 diabetic rats showed significantly altered PK behaviors of genipin, geniposide and geniposidic acid (especially systemic exposure, AUCs of genipin, geniposide and geniposidic acid). Online MD-UPLC-MS/MS provides real-time sampling and monitoring, these functions can be applied to PKs of iridoids from G. jasminoides.