title: Characterization of metabolites in rats after intravenous administration of salvianolic acid for injection by ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry.
abstract: It is an essential requirement to clarify the metabolites of traditional Chinese medicine (TCM) injections, which contain numerous ingredients, to assess their safe and effective use in clinic. Salvianolic acid for injection (SAFI), made from hydrophilic phenolic acids in Salvia miltiorrhiza Bunge, has been widely used for the treatment of cerebrovascular diseases, but information on its metabolites in vivo is still lacking. In the present study, we aimed to holistically characterize the metabolites of the main active ingredients in rat plasma, bile, urine and feces following intravenous administration of SAFI. An ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method was developed. Combining information on retention behaviors, multistage mass spectra and literature data, a total of eight prototypes and 52 metabolites were tentatively characterized. Metabolites originated from rosmarinic acid and salvianolic acid B comprised the majority of identified compounds. Meanwhile, four metabolites derived from salvianolic acid D and five from salvianolic acid B are reported for the first time. This study revealed that methylation, sulfation and glucuronidation were the major metabolic pathways of phenolic acids in SAFI in vivo. Furthermore, the developed UPLC/Q-TOF-MS method could also benefit the metabolic investigation of extracts and preparations in TCM with hydrophilic ingredients. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
authors.forename: Jingzhuo
authors.initials: J
authors.lastname: Miao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
authors.forename: Wanyang
authors.initials: W
authors.lastname: Sun
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Holding Group Co., Ltd., Tianjin, 300402, People's Republic of China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Huang
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Holding Group Co., Ltd., Tianjin, 300402, People's Republic of China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Holding Group Co., Ltd., Tianjin, 300402, People's Republic of China.
authors.forename: Shuming
authors.initials: S
authors.lastname: Li
authors.affiliation: Qinghai Provincial Institute for Food and Drug Control, Xining, 810016, People's Republic of China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Han
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Holding Group Co., Ltd., Tianjin, 300402, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Tong
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Sun
mesh_terms: D061605:Administration, Intravenous; D000475:Alkenes / Q000008:administration & dosage*; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D057230:Limit of Detection; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D059808:Polyphenols / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000475:Alkenes; D059808:Polyphenols; C568740:salvianolic acid
keywords: UPLC/Q-TOF-MS; metabolites in vivo; rat; salvianolic acid for injection