title: Comparative pharmacokinetic analysis of extracts of crude and wine-processed Dipsacus asper in rats by a sensitive ultra performance liquid chromatography-tandem mass spectrometry approach.
abstract: The purpose of this study is to establish and validate an UPLC-MS/MS approach to determine 4-caffeoylquinic acid, chlorogenic acid, 3,5-dicaffeoylquinic acid, loganic acid, loganin, sweroside, dipsacoside B and asperosaponin VI from extracts of crude and wine-processed Dipsacus asper in biological samples and apply the approach to a comparative pharmacokinetic study. A Waters BEH C18UPLC column was employed with acetonitrile/0.2% formic acid-water as mobile phases. The mass analysis was carried out in a triple quadrupole mass spectrometer using multiple reaction monitoring (MRM) with negative scan mode. A one-step protein precipitation by acetonitrile was performed to extract the eight analytes from plasma. Our results revealed that all of the calibration curves displayed good linear regression (r2>0.9990). The lower limits of quantification (LLOQ) were determined as 10.0, 9.6, 8.9, 9.1, 9.2, 9.8, 10.1 and 9.8ng/mL. The intra-day and inter-day precisions (RSD) of the eight compounds at high, medium and low levels were less than 4.94% and the bias of the accuracies ranged from -3.89% to 3.95%.The extraction recoveries of the eight compounds were from 90.4% to 100.2% and the matrix effects ranged from 89.3% to 100.1%. The stabilities of these compounds were investigated by analyzing six replicates of QC samples at three different concentrations following storage at 25°C for 4h, -80°C for 30days, three-freeze-thaw cycles, and 4°C for 24h. All the samples showed satisfactory precision and accuracy after various stability tests. Pharmacokinetic parameters were estimated using a non-compartment model. Compared with the crude group, the parameters of Cmaxand AUC0-tof 4-caffeoylquinic acid, loganic acid, loganin and asperosaponin VI increased remarkably (p<0.05) after oral administration of the aqueous extract of wine-processed Dipsacus asper, indicating that wine-processing could enhance bioavailability of 4-caffeoylquinic acid, loganic acid, loganin and asperosaponin VI.
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: taoyi1985812@126.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tao
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yuchao
authors.initials: Y
authors.lastname: Ren
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Baochang
authors.initials: B
authors.lastname: Cai
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Liuqing
authors.initials: L
authors.lastname: Di
authors.affiliation: Department of Microbiology and Immunology, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Shi
authors.affiliation: State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 201203, PR China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Hu
mesh_terms: D000818:Animals; D002726:Chlorogenic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D049917:Dipsacaceae / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000032:analysis / Q000302:isolation & purification / Q000493:pharmacokinetics; D057888:Iridoid Glucosides / Q000032:analysis / Q000097:blood / Q000302:isolation & purification; D039823:Iridoids / Q000032:analysis / Q000097:blood / Q000302:isolation & purification; D057230:Limit of Detection; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood / Q000302:isolation & purification; D010936:Plant Extracts / Q000032:analysis / Q000097:blood* / Q000302:isolation & purification; D011801:Quinic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000032:analysis / Q000097:blood / Q000302:isolation & purification; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014920:Wine / Q000032:analysis
chemical_list: D004365:Drugs, Chinese Herbal; D057888:Iridoid Glucosides; D039823:Iridoids; D010936:Plant Extracts; D012503:Saponins; C534004:akebia saponin D; C472707:caffeoylquinic acid; D011801:Quinic Acid; C002947:loganic acid; D002726:Chlorogenic Acid; C083461:dipsacoside B; D009828:Oleanolic Acid; C059516:loganin; C049412:sweroside; C100434:3,5-dicaffeoylquinic acid
keywords: Dipsacus asper; Pharmacokinetics; UPLC–MS/MS; Wine-processed