title: Simultaneous determination of two iridoid glycosides, two anthraquinones and four flavonoid glycosides of Zhi-Zi-Da-Huang decoction in rat plasma by UFLC-MS/MS: application to a comparative pharmacokinetic study in normal and cholestatic liver injury rats.
abstract: A selective, sensitive and reliable ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed for the simultaneous determination of two iridoid glycosides (geniposide and genipin gentiobioside), two anthraquinones (rhein and emodin) and four flavonoid glycosides (isonaringin, naringin, hesperidin and neohesperidin), the major active ingredients of Zhi-Zi-Da-Huang decoction (ZZDHD), in rat plasma using paeoniflorin as internal standard (IS). After liquid-liquid extraction with ethyl acetate-isopropanol (1:1, v/v), separation was achieved on a Shim-pack XR-ODS C18 column (75 mm×3.0 mm, 2.2 μm) using gradient elution with a mobile phase consisting of water (containing 0.1% formic acid) and acetonitrile at a flow rate of 0.4 mL/min. Detection was performed on 4000 QTRAP mass spectrometry equipped with turbo ion spray source in the negative ionization and multiple reaction monitoring (MRM) mode. The intra- and inter-day precisions (as relative standard deviation) were less than 11.4%, and accuracy (as relative error) was within ± 10.0%. The lower limits of quantification (LLOQ) were 4.0, 0.5, 2.0, 0.1, 1.0, 2.0, 1.0, 2.0 ng/mL for geniposide, genipin gentiobioside, rhein, emodin, isonaringin, naringin, hesperidin and neohesperidin, respectively. The extraction recoveries of the analytes and IS from rat plasma were all more than 86.0%. The method was fully validated and applied to compare the pharmacokinetic profiles of the analytes in normal and cholestatic liver injury (CLI) rats after oral administration of ZZDHD. Results showed that there were remarkable differences in pharmacokinetic properties of the analytes between normal and CLI group.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China; School of Pharmacy, Jilin Medical College, 5 Jilin Street, Fengman District, Jilin 132013, China.
authors.forename: Heyun
authors.initials: H
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Kaishun
authors.initials: K
authors.lastname: Bi
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Han
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China; School of Pharmacy, Jilin Medical College, 5 Jilin Street, Fengman District, Jilin 132013, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Guan
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Kelin
authors.initials: K
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Longshan
authors.initials: L
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: yinran_syphu@163.com.
authors.forename: Ran
authors.initials: R
authors.lastname: Yin
authors.affiliation: School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: houxiaohong@syphu.edu.cn.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Hou
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002780:Cholestasis, Intrahepatic / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004355:Drug Stability; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005419:Flavonoids / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D057889:Iridoid Glycosides / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; 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
chemical_list: D000880:Anthraquinones; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D057889:Iridoid Glycosides
keywords: Cholestatic liver injury; Pharmacokinetics; Rat plasma; UFLC-MS/MS; Zhi-Zi-Da-Huang decoction