title: Simultaneous quantification of Kirenol and ent-16β,17-dihydroxy-kauran-19-oic acid from Herba Siegesbeckiae in rat plasma by liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic studies.
abstract: A rapid and specific liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the simultaneous determination of two active diterpenoids: Kirenol and ent-16β,17-dihydroxy-kauran-19-oic acid (DHKA) from Herba Siegesbeckiae in rat plasma using osthole as an internal standard (IS). Plasma sample pretreatment involved a one-step liquid-liquid extraction with ethyl acetate. Chromatographic separation was performed on a Waters Symmetry C18 column (2.1mm×100mm, 3.5μm) with isocratic elution using methanol-5mmol/L aqueous ammonium acetate (80:20, v/v) as the mobile phase at a flow rate of 0.2mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode under positive and negative electrospray ionization. The calibration curves were linear over the range of 50.0-25,000ng/mL for Kirenol, and 25.0-12,500ng/mL for DHKA. The extraction recoveries of the two analytes and the IS were all over 85%. The intra- and inter-day precision (relative standard deviation) values were less than 16.8% and the accuracy (relative error) ranged from -10.7 to 10.6% at four quality control levels. The validated method was successfully applied to a comparative pharmacokinetic study of the two diterpenoids in rat plasma after intragastric administration of Kirenol, DHKA and Herba Siegesbeckiae extract. The results showed that there were obvious differences between the pharmacokinetic behaviors after oral administration of Herba Siegesbeckiae extract compared with each of the substances alone.
authors.affiliation: Department of Analytical Chemistry, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, PR China.
authors.forename: Linan
authors.initials: L
authors.lastname: Huo
authors.forename: Zhen
authors.initials: Z
authors.lastname: Jiang
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
authors.forename: Xintao
authors.initials: X
authors.lastname: Wang
authors.forename: Xingjie
authors.initials: X
authors.lastname: Guo
mesh_terms: D000818:Animals; D019659:Asteraceae / Q000737:chemistry*; D002853:Chromatography, Liquid / Q000379:methods*; D003374:Coumarins / Q000097:blood / Q000737:chemistry; D004224:Diterpenes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D045786:Diterpenes, Kaurane / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D016014:Linear Models; D008297:Male; D010936:Plant Extracts / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D003374:Coumarins; D004224:Diterpenes; D045786:Diterpenes, Kaurane; D010936:Plant Extracts; C560087:kirenol; C046627:osthol
keywords: Herba Siegesbeckiae; Kirenol; LC-ESI–MS/MS; Pharmacokinetics; ent-16β,17-dihydroxy-kauran-19-oic acid