title: UFLC-MS/MS method for simultaneous determination of six lignans of Schisandra chinensis (Turcz.) Baill. in normal and insomniac rats brain microdialysates and homogenate samples: towards an in-depth study for its sedative-hypnotic activity.
abstract: Schisandra chinensis (Turcz.) Baill., a traditional Chinese medicine, has been clinically used for the treatment of insomnia for centuries. The insomnia mechanism and the possible active ingredients of S. chinensis remain largely unknown. The objective of this study was to develop a method to detect its components which could pass through the blood brain barrier (BBB) by determining the brain microdialysate and brain tissue homogenate samples and then obtain the pharmacokinetic profile in brain for comprehensive understanding of its hypnotic clinical efficacy. Therefore, an efficient, sensitive and selective ultra fast liquid chromatography/tandem mass spectrometry method for the simultaneous determination of six sedative and hypnotic lignans (schisandrin, schisandrol B, schisantherin A, deoxyshisandrin, γ-schisandrin and gomisin N) of Schisandra chinensis (Turcz.) Baill. in rat brain tissue homogenate and brain microdialysates has been developed and validated. The analysis was performed on a Shim-pack XR-ODS column (75 mm × 3.0 mm, 2.2 µm) using gradient elution with the mobile phase consisting of acetonitrile and 0.1% formic acid water. The method was validated in brain homogenate and microdialysate samples, which all showed good linearity over a wide concentration range (r(2)> 0.99), and the obtained lower limit of quantification was 0.1 ng · ml(-1) for the analytes in brain microdialysate samples. The intra- and inter-day assay variability was less than 15% for all analytes. The study proved the six lignans, as sedative and hypnotic ingredients, could pass through the BBB with brain targeting, distributed mainly in the hypothalamus and possessed complete pharmacokinetics process in brain. The results also indicated that significant difference in pharmacokinetic parameters of the analytes was observed between two groups, while absorptions of these analytes in insomniac group were significantly better than those in normal group.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Wei
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Ronghua
authors.initials: R
authors.lastname: Fan
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.forename: Xiuli
authors.initials: X
authors.lastname: Ou
authors.forename: Kelin
authors.initials: K
authors.lastname: Chen
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Jia
authors.forename: Kaishun
authors.initials: K
authors.lastname: Bi
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004355:Drug Stability; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D006993:Hypnotics and Sedatives; D017705:Lignans / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D016014:Linear Models; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D032141:Schisandra / Q000737:chemistry*; D012680:Sensitivity and Specificity; D007319:Sleep Initiation and Maintenance Disorders / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D004365:Drugs, Chinese Herbal; D006993:Hypnotics and Sedatives; D017705:Lignans