title: Study on the pharmacokinetics and metabolism of costunolide and dehydrocostus lactone in rats by HPLC-UV and UPLC-Q-TOF/MS.
abstract: A method based on high-performance liquid chromatography coupled with ultraviolet detection was developed for studying the pharmacokinetics of costunolide (Cos) and dehydrocostus lactone (Dehy) in rats after intravenous (i.v.) administration. Following i.v. administration, the maximum plasma concentrations of Cos and Dehy were observed to be 12.29 ± 1.47 and 5.79 ± 0.13 µg/mL, respectively. The bioavailability of Cos was larger than that of Dehy; however, the clearance and the volume of distribution of Dehy were much larger than those of Cos. An ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry system with automated MS(E) (E represents collision energy) data analysis software (MetaboLynx(TM)) was used to analyze and identify the metabolites of Cos and Dehy in vivo. Four metabolites of Cos and six metabolites of Dehy were discovered from the plasma, urine and feces of rats. The main metabolic pathway of Cos was phase II biotransformation, but the main metabolic pathways of Dehy was phase І biotransformation. Two sequential desaturations and N-acetylcysteine conjugation were the common metabolic pathways of Cos and Dehy in rats. This information may be useful for the further development of the two drug candidates.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Zhangxiao
authors.initials: Z
authors.lastname: Peng
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Xue
authors.initials: X
authors.lastname: Gu
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Guo
authors.forename: Chao
authors.initials: C
authors.lastname: Yan
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005243:Feces / Q000737:chemistry; D007783:Lactones / Q000032:analysis / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D013058:Mass Spectrometry / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012717:Sesquiterpenes / Q000032:analysis / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*
chemical_list: D007783:Lactones; D012717:Sesquiterpenes; C083030:dehydrocostus lactone; C002602:costunolide
keywords: costunolide; dehydrocostus lactone; metabolites; pharmacokinetics; ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry