title: Simultaneous determination of ten compounds in rat plasma by UPLC-MS/MS: Application in the pharmacokinetic study of Ma-Zi-Ren-Wan.
abstract: Ma-Zi-Ren-Wan (MZRW) is a classic Chinese formula which has been used to treat human constipation in China for over 2000 years. In order to make good and rational use of this formula in the future, this paper presents the first attempt to track the pharmacokinetic features of MZRW in rat using rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Ten chemical components of MZRW, namely, rhein, emodin, aloe emodin, hesperidin, naringin, amygdalin, albiflorin, paeoniflorin, magnolol and honokiol, were simultaneously determined in rat plasma after a single oral administration (10g/kg body weight) of MZRW to rats. Geniposide and liquiritin were used as internal standards. The separation was performed on a Waters ACQUITY BEH C18 column (100mm×2.1mm, 1.7μm). The detection was conducted by multiple-reaction monitoring (MRM) in negative ionization mode. Two highest abundant MRM transitions without interference were optimized for each analyte. This method was well validated in terms of linearity, precision, accuracy, recovery, matrix effect and stability. All calibration curves had good linearity (r(2)>0.995) over the concentration range from 3.9 to 125.0ng/mL for emodin, 3.9-500.0ng/mL for amygdalin, 2.0-4000.0ng/mL for naringin and hesperidin, 3.9-2000.0ng/mL for magnolol, 7.8-2000.0ng/mL for rhein and 3.9-4000.0ng/mL for albiflorin, paeoniflorin, aloe emodin and honokiol. The intra-day and inter-day precision (relative standard deviation) was within 15%, the accuracy (relative error) ranged from -13.6% to 15.1%, and the lower limit of quantification in plasma ranged between 2.0ng/mL and 7.8ng/mL. Extraction recovery, matrix effect and stability were satisfactory. The validated method was successfully applied to a pharmacokinetic study of these ten compounds after oral administration of MZRW to rats. The pharmacokinetic parameters of each compound can facilitate clinical studies in the future.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China; Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Hu
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Quan-Bin
authors.initials: QB
authors.lastname: Han
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Linda Li-Dan
authors.initials: LL
authors.lastname: Zhong
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Li
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Hing-Man
authors.initials: HM
authors.lastname: Ho
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China; Guangzhou Research Institute of Snake Venom, Guangzhou Medical University, Guangzhou 510000, China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Shu-Hai
authors.initials: SH
authors.lastname: Lin
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China; First School of Clinic Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510000, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Mi
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China.
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Tan
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China. Electronic address: xuhongxi88@gmail.com.
authors.forename: Hong-Xi
authors.initials: HX
authors.lastname: Xu
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. Electronic address: bzxiang@hkbu.edu.hk.
authors.forename: Zhao-Xiang
authors.initials: ZX
authors.lastname: Bian
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D001713:Biphenyl Compounds; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005419:Flavonoids / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D006027:Glycosides / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D017705:Lignans; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000880:Anthraquinones; D001713:Biphenyl Compounds; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D006027:Glycosides; D017705:Lignans; C005498:magnolol; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: Active ingredient; Ma-Zi-Ren-Wan; Pharmacokinetics; Rat plasma; UPLC-MS/MS