title: Dual ultrasonic-assisted dispersive liquid-liquid microextraction coupled with microwave-assisted derivatization for simultaneous determination of 20(S)-protopanaxadiol and 20(S)-protopanaxatriol by ultra high performance liquid chromatography-tandem mass spectrometry.
abstract: This paper, for the first time, reported a speedy hyphenated technique of low toxic dual ultrasonic-assisted dispersive liquid-liquid microextraction (dual-UADLLME) coupled with microwave-assisted derivatization (MAD) for the simultaneous determination of 20(S)-protopanaxadiol (PPD) and 20(S)-protopanaxatriol (PPT). The developed method was based on ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) detection using multiple-reaction monitoring (MRM) mode. A mass spectrometry sensitizing reagent, 4'-carboxy-substituted rosamine (CSR) with high reaction activity and ionization efficiency was synthesized and firstly used as derivatization reagent. Parameters of dual-UADLLME, MAD and UHPLC-MS/MS conditions were all optimized in detail. Low toxic brominated solvents were used as extractant instead of traditional chlorinated solvents. Satisfactory linearity, recovery, repeatability, accuracy and precision, absence of matrix effect and extremely low limits of detection (LODs, 0.010 and 0.015ng/mL for PPD and PPT, respectively) were achieved. The main advantages were rapid, sensitive and environmentally friendly, and exhibited high selectivity, accuracy and good matrix effect results. The proposed method was successfully applied to pharmacokinetics of PPD and PPT in rat plasma.
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China; National Center for Mass Spectrometry in Changchun & Key Laboratory for Traditional Chinese Medicine Chemistry and Mass Spectrometry of Jilin Province, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, PR China; Qinghai Key Laboratory of Qinghai-Tibet Plateau Biological Resources & Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining, Qinghai 810001, PR China. Electronic address: xianenzhao@163.com.
authors.forename: Xian-En
authors.initials: XE
authors.lastname: Zhao
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China; Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, Fujian, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Lv
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Qu
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China.
authors.forename: Guang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China.
authors.forename: Yongrui
authors.initials: Y
authors.lastname: He
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Wei
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Li
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China.
authors.forename: Lian
authors.initials: L
authors.lastname: Xia
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China.
authors.forename: Shijuan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China. Electronic address: jmyou6304@163.com.
authors.forename: Jinmao
authors.initials: J
authors.lastname: You
authors.affiliation: National Center for Mass Spectrometry in Changchun & Key Laboratory for Traditional Chinese Medicine Chemistry and Mass Spectrometry of Jilin Province, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, PR China.
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
authors.affiliation: National Center for Mass Spectrometry in Changchun & Key Laboratory for Traditional Chinese Medicine Chemistry and Mass Spectrometry of Jilin Province, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, PR China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Qinghai Key Laboratory of Qinghai-Tibet Plateau Biological Resources & Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining, Qinghai 810001, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: National Center for Mass Spectrometry in Changchun & Key Laboratory for Traditional Chinese Medicine Chemistry and Mass Spectrometry of Jilin Province, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, PR China.
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D057230:Limit of Detection; D059627:Liquid Phase Microextraction; D008872:Microwaves; D051381:Rats; D012502:Sapogenins / Q000097:blood*; D012997:Solvents / Q000737:chemistry; D053719:Tandem Mass Spectrometry; D014465:Ultrasonics
chemical_list: D012502:Sapogenins; D012997:Solvents; C081552:protopanaxatriol; C062916:protopanaxadiol
keywords: 20(S)-protopanaxadiol; 20(S)-protopanaxatriol; Dispersive liquid–liquid microextraction; Mass spectrometry sensitization; Microwave-assisted derivatization; Pharmacokinetics