title: 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.
abstract: 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 Tmaxand 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.
authors.affiliation: National Center of Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; University of Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Xueju
authors.initials: X
authors.lastname: Zhang
authors.affiliation: National Center of Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; University of Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: National Center of Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: National Center of Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China. Electronic address: songfr@ciac.ac.cn.
authors.forename: Zifeng
authors.initials: Z
authors.lastname: Pi
authors.affiliation: National Center of Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: National Center of Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China. Electronic address: mslab21@ciac.ac.cn.
authors.forename: Fengrui
authors.initials: F
authors.lastname: Song
mesh_terms: D000818:Animals; D002681:China; D002853:Chromatography, Liquid; D048909:Diabetes Complications; D003921:Diabetes Mellitus, Experimental; D032062:Gardenia; D039823:Iridoids; D017551:Microdialysis; D051381:Rats; D053719:Tandem Mass Spectrometry
chemical_list: D039823:Iridoids
keywords: Gardenia jasminoides Ellis; Online mircrodilysis; Pharmacokinetics; Type 2 diabetes mellitus; UPLC–MS/MS; Unbound iridoids