title: Systematic identification of shikonins and shikonofurans in medicinal Zicao species using ultra-high performance liquid chromatography quadrupole time of flight tandem mass spectrometry combined with a data mining strategy.
abstract: Shikonin, shikonofuran and their derivatives are the main bioactive components of Zicao, a traditional Chinese herbal medicine prepared with the dried roots of Lithospermum erythrorhizon, Arnebia euchroma or Arnebia guttata. However, approaches on the systematic discovery and identification of shikonins and shikonofurans, especially unknown ones, are still not available. To address this issue, the gas-phase CID-fragmentation routes for the shikonins and shikonofurans were established by using ESI-QTOF-MS in the negative ion mode and low-energy collision induced dissociation tandem mass spectrometry (CID-MS/MS) in this study using seventeen standards. As a result, diagnostic product ions for rapid discovery and classification of shikonins and shikonofurans were determined. In addition, various mobile phase compositions and UHPLC elution programs were evaluated to achieve optimal separation efficiency and detection response of these types of analytes. Based on these findings, an integral approach using UHPLC-ESI-QTOF-MS and CID-MS/MS analyses together with a novel two steps data mining strategy was developed for systematic analysis of shikonins and shikonofurans in complex samples. Consequently, 58 compounds including 32 novel ones were efficiently discovered and identified from the crude extract of Zicao. Moreover, comparative analyses of the 58 chemical components in three Zicao species including Lithospermum erythrorhizon, Arnebia euchroma and Arnebia guttata samples were conducted using the established analytical method, which can be instructive for future utilization of Zicao and its related medicinal products.
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430030, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Liao
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430030, China.
authors.forename: Aiqian
authors.initials: A
authors.lastname: Li
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430030, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
authors.affiliation: Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ouyang
authors.affiliation: Department of Pharmacy, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430030, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Medical Research Center, Humanwell Healthcare (Group) Co., Ltd., 666 Gao xin Road, Wuhan, Hubei 430075, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430030, China. Electronic address: jianghongliang@hust.edu.cn.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Jiang
mesh_terms: D002851:Chromatography, High Pressure Liquid; D057225:Data Mining; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification*; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification*; D053719:Tandem Mass Spectrometry
chemical_list: D004365:Drugs, Chinese Herbal; D005663:Furans; D009285:Naphthoquinones; C016101:shikonin
keywords: Data mining strategy; Shikonin/shikonofuran; Structural identification; UHPLC-ESI-QTOF-MS; Zicao