title: An LC-MS method for simultaneous determination of five iridoids from Zhi-zi-chi Decoction in rat brain microdialysates and tissue homogenates: towards an in depth study for its antidepressive activity.
abstract: Zhi-zi-chi Decoction has been clinically utilized for the treatment of depression for more than thousand years. In order to investigate the possible bioactive components that could pass through the blood brain barrier (BBB) and the mechanism of antidepressant, a sensitive LC-MS method was developed to detect the ingredients (geniposide, scandoside methyl ester, gardenoside, deacetyl asperulosidic acid methyl ester and genipin-1-β-gentiobioside) in rat brain microdialysates and tissue homogenates samples (hippocampus, hypothalamus, premotor cortex, striatum, oblongata and cerebellum). Method development and validation are described in terms of calibration curves, extraction yield, lower limit of quantification (LLOQ), precision, accuracy, intra- and inter-day variability, which are in accordance with the requirements. Microdialysis in hippocampus demonstrated that the five iridoids possessed complete pharmacokinetic process while brain tissue homogenate method testified the distribution regularity in brain. The work clarified that the five iridoids, as antidepressant ingredients, could pass through the BBB, distribute targeted and possess complete pharmacokinetics in brain. These observations, along with the large database of rat brain microdialysates and tissue homogenates data, could enable future efforts aimed to improve our understanding of the relationship between bioactive ingredients and clinical therapy of depression.
authors: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors: Kankan
authors: K
authors: Qu
authors: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors: Longshan
authors: L
authors: Zhao
authors: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors: Xinyi
authors: X
authors: Luo
authors: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Chenning
authors: C
authors: Zhang
authors: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors: Pengyi
authors: P
authors: Hou
authors: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors: Kaishun
authors: K
authors: Bi
authors: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address: cxh_syphu@hotmail.com.
authors: Xiaohui
authors: X
authors: Chen
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002853:Chromatography, Liquid / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D039823:Iridoids / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D016014:Linear Models; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D004365:Drugs, Chinese Herbal; D039823:Iridoids
keywords: Brain microdialysate; Brain tissue homogenates; Iridoids; LC–MS; Zhi-zi-chi Decoction