title: Metabolites identification of Huo Luo Xiao Ling Dan in rat urine by UPLC coupled with electrospray ionization time-of-flight mass spectrometry.
abstract: Huo Luo Xiao Ling Dan (HLXLD), a Chinese herbal formula, is used in folk medicine for the treatment of arthritis and other chronic inflammatory diseases. However, the in vivo integrated metabolism of its multiple components remains unknown. In this paper, an ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) method was developed for detection and identification of HLXLD metabolites in rat urine at high and normal clinical dosages. The prototype constituents and their metabolites in urine were analyzed. The mass measurements were accurate within 8 ppm, and subsequent fragment ions offered higher quality structural information for interpretation of the fragmentation pathways of various compounds. A total of 85 compounds were detected in high dosages urine samples by a highly sensitive extracted ion chromatograms method, including 31 parent compounds and 54 metabolites. Our results indicated that phase 2 reactions (e.g. glucuronidation, glutathionidation and sulfation) were the main metabolic pathways of lactones, alkaloids and flavones, while phase I reactions (e.g. hydrogenation and hydroxylation) were the major metabolic reaction for coumarins, paeoniflorin and iridoids. This investigation provided important structural information on the metabolism of HLXLD and provided scientific evidence to obtain a more comprehensive metabolic profile.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Fenrong
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ai
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Qiaoxia
authors.initials: Q
authors.lastname: Bian
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Ma
authors.affiliation: Mailman Research Center, McLean Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: David Y-W
authors.initials: DY
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Dai
mesh_terms: D000470:Alkaloids / Q000378:metabolism / Q000652:urine; D000818:Animals; D001578:Benzopyrans / Q000378:metabolism / Q000652:urine*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D007783:Lactones / Q000378:metabolism / Q000652:urine; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000470:Alkaloids; D001578:Benzopyrans; D004365:Drugs, Chinese Herbal; D007783:Lactones; C547651:huo luo xiao ling dan
keywords: Huo Luo Xiao Ling Dan; UPLC-ESI-Q-TOF-MS; metabolites in vivo; urine