An untargeted metabolomics-driven approach based on LC-TOF/MS and LC-MS/MS for the screening of xenobiotics and metabolites of Zhi-Zi-Da-Huang decoction in rat plasma.
Zhi-Zi-Da-Huang decoction (ZZDHD), a typical traditional Chinese medicine prescription, is widely used in clinical practice for the treatment of alcoholic liver disease. However, due to lack of holistic metabolic research, the active ingredients of ZZDHD have not been fully elucidated. It entails a huge obstacle for the quality evaluation, pharmacokinetic studies and clinical-safe medication administration of ZZDHD. In this work, an untargeted metabolomics-driven approach was proposed to rapidly screen and characterize xenobiotics and related metabolites in vivo conducted by LC-TOF/MS and LC-QqQ/MS. The tR-m/z pairs which were present in the ZZDHD-dosed group and absent in the control group could be clearly displayed by XCMS Online platform combined with supervised orthogonal partial least squares discriminant analysis. Among them, a total of 61 ZZDHD-related xenobiotics and metabolites including 34 prototype components and 27 metabolites were rapidly identified or tentatively characterized in rat plasma. The results indicated that iridoid glycosides and monoterpenoids from Gardenia jasminoides Ellis, flavonoid glycosides from Citrus aurantium L., as well as anthraquinones from Rheum palmatum L. were the main absorbed chemical components of ZZDHD. Hydrolysis, glucuronidation and sulfation were the main metabolic pathways of ZZDHD in vivo. The present study provided a solid basis for further revealing the relationship between the xenobiotic metabolome and pharmacological activity of ZZDHD. In addition, the application of untargeted metabolomics-driven approach offers a fresh insight for rapid screening and identifying xenobiotics and metabolites of ZZDHD and other multiherb prescription.
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Huan
H
Wu
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Xixi
X
Li
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Xuemei
X
Yan
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Li
L
An
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Kaiwen
K
Luo
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Mingjing
M
Shao
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Yue
Y
Jiang
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Rui
R
Xie
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing 210009, China. Electronic address: fengfang1@126.com.
Fang
F
Feng
D000284:Administration, Oral; D000818:Animals; D000880:Anthraquinones / Q000097:blood; D002853:Chromatography, Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000032:analysis* / Q000302:isolation & purification / Q000378:metabolism / Q000493:pharmacokinetics; D005419:Flavonoids / Q000097:blood; D057889:Iridoid Glycosides / Q000097:blood; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000295:instrumentation / Q000379:methods*; D010946:Plants, Medicinal / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*; D015262:Xenobiotics / Q000097:blood*
D000880:Anthraquinones; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D057889:Iridoid Glycosides; D015262:Xenobiotics; C000608599:zhi-zi-da-huang
LC–ESI–QqQ/MS; LC–ESI–TOF/MS; Metabolites; Untargeted metabolomics; Xenobiotics; Zhi-Zi-Da-Huang decoction