title: Simultaneous Determination of Three Furanocoumarins by UPLC/MS/MS: Application to Pharmacokinetic Study of Angelica dahurica Radix after Oral Administration to Normal and Experimental Colitis-Induced Rats.
abstract: In traditional oriental medicine,Angelica dahuricaRadix (ADR) is used in the treatment of gastrointestinal, respiratory, neuromuscular, and dermal disorders. We evaluated the pharmacokinetic profiles of oxypeucedanin, imperatorin, and isoimperatorin, major active ingredients of ADR, in normal and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rats. A rapid, sensitive, and validated UPLC/MS/MS method was established for evaluating the pharmacokinetics of three furanocoumarins. After oral administration of ADR (0.5 and 1.0 g/kg), blood samples were collected periodically from the tail vein. In colitis rats, the time to reach the peak concentration (Tmax) of imperatorin and isoimperatorin was significantly delayed (p< 0.05). Lower peak plasma concentrations (Cmax) and longer mean residence times for all furanocoumarins were also observed (p< 0.05) compared with normal rats. There was no significant difference in the area under the plasma concentration-time curve or elimination half-lives. Thus, the delayed Tmaxand decreased Cmax, with no influence on the elimination half-life, could be colitis-related changes in the drug-absorption phase. Therefore, the prescription and use of ADR in colitis patients should receive more attention.
authors.affiliation: KM Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Korea. hyhhwang@kiom.re.kr.
authors.forename: Youn-Hwan
authors.initials: YH
authors.lastname: Hwang
authors.affiliation: KM Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Korea. hjyang@kiom.re.kr.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: KM Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Korea. jyma@kiom.re.kr.
authors.forename: Jin Yeul
authors.initials: JY
authors.lastname: Ma
mesh_terms: D029969:Angelica / Q000737:chemistry; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003092:Colitis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D004195:Disease Models, Animal; D004355:Drug Stability; D011564:Furocoumarins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D008297:Male; D015394:Molecular Structure; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
chemical_list: D011564:Furocoumarins; D010936:Plant Extracts
keywords: Angelica dahurica Radix; colitis; imperatorin; isoimperatorin; oxypeucedanin; pharmacokinetics