title: Simultaneous determination of osthole, bergapten and isopimpinellin in rat plasma and tissues by liquid chromatography-tandem mass spectrometry.
abstract: A highly selective and sensitive method for simultaneous quantitation of osthole, bergapten and isopimpinellin in rat plasma and tissues was developed by liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS). After liquid-liquid extraction of samples with methyl tert-butyl ether, the analytes and dextrorphan (internal standard, IS) were separated by a Hypersil GOLD AQ C18 column with gradient elution of acetonitrile and water containing 0.5‰ formic acid. Three determinands were detected using an electrospray ionization (ESI) tandem mass spectrometry in the multiple reaction monitoring (MRM) modes with positive electrospray ionization. Calibration curves were recovered over the concentration ranges of 1-200 ng/ml, 1-500 ng/ml, 0.25-200 ng/ml for osthole, bergapten and isopimpinellin in plasma; 1-100 ng/ml, 1-500 ng/ml, 0.5-100 ng/ml for osthole, bergapten and isopimpinellin in tissues, respectively. The intra-day precision (R.S.D.) was within 13.90% and the intra-day accuracy (R.E.) was within -6.27 to 6.84% in all biological matrixes. The inter-day precision (R.S.D.) was less than 13.66% and the inter-day accuracy (R.E.) was within -10.64 to 13.04%. Then the method was successfully applied to investigate plasma pharmacokinetic study and tissue distribution of osthole, bergapten and isopimpinellin in rats after oral administration of Fructus Cnidii extraction, especially for testis/uterus tissue distribution. The results demonstrated that osthole, bergapten and isopimpinellin were absorbed and eliminated rapidly with wide distributions in rats. Distribution data of these three bioactive components in testis/uterus tissues could offer useful information for the further preclinical and clinical studies of Fructus Cnidii in the treatment of genital system disease.
authors.affiliation: School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing 210009, People's Republic of China; School of Life Science & Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 210009, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing 210009, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.affiliation: School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing 210009, People's Republic of China. Electronic address: nancyzhang03@hotmail.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing 210009, People's Republic of China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing 210009, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Sun
authors.affiliation: School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing 210009, People's Republic of China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Tang
authors.affiliation: School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing 210009, People's Republic of China.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Cui
authors.affiliation: School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing 210009, People's Republic of China.
authors.forename: Di
authors.initials: D
authors.lastname: Yao
authors.affiliation: School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing 210009, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing 210009, People's Republic of China.
authors.forename: Guiying
authors.initials: G
authors.lastname: Gu
authors.affiliation: School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing 210009, People's Republic of China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhu
authors.affiliation: School of Life Science & Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 210009, People's Republic of China. Electronic address: weiping@njtech.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.affiliation: School of Life Science & Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 210009, People's Republic of China.
authors.forename: Pingkai
authors.initials: P
authors.lastname: Ouyang
mesh_terms: D000078223:5-Methoxypsoralen; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D003374:Coumarins / Q000032:analysis / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D011564:Furocoumarins / Q000032:analysis / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D016014:Linear Models; D008297:Male; D008730:Methoxsalen / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D003374:Coumarins; D011564:Furocoumarins; C015304:isopimpinellin; D000078223:5-Methoxypsoralen; D008730:Methoxsalen; C046627:osthol
keywords: Bergapten; Isopimpinellin; LC–MS/MS; Osthole; Pharmacokinetics; Tissue distribution