title: Rapid determination of isocorydine in rat plasma and tissues using liquid chromatography--tandem mass spectrometry and its applications to pharmacokinetics and tissue distribution.
abstract: A rapid and sensitive method for the determination of isocorydine in rat plasma and tissues was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The biological samples were processed by extracting with diethyl ether-dichloromethane (3:2, v/v) and tetrahydropulmatine was used as the internal standard (IS). Detection of the analytes was achieved using positive ion mode electrospray ionization in the multiple reaction monitoring mode. The MS/MS ion transitions monitored were m/z 342.0→279.0 and 356.0→191.9 for isocorydine and IS, respectively. The maximum plasma concentration (C(max) 2496.8 ± 374.4 µg/L) was achieved at 0.278 ± 0.113 h (T(max)) and the half-life (t(1/2)) of isocorydine was 0.906 ± 0.222 h after a 20 mg/kg oral administration. As for a 2 mg/kg intravenous (i.v.) administration, the C(max) and clearance (CL) were 1843.3 ± 338.3 µg/L and 2.381 ± 0.356 L/h/kg, respectively. Based on the AUC(0-∞) obtained from oral and i.v. administration, the absolute bioavailability (F) was estimated as 33.4%. Tissue distribution results indicated that isocorydine underwent a rapid and wide distribution into tissues and it could effectively cross the blood-brain barrier.
authors.affiliation: Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Changchuan
authors.initials: C
authors.lastname: Guo
authors.forename: Caihong
authors.initials: C
authors.lastname: Yu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Wang
authors.forename: Shengjia
authors.initials: S
authors.lastname: Wang
authors.forename: Weihong
authors.initials: W
authors.lastname: Wang
authors.forename: Haihong
authors.initials: H
authors.lastname: Hu
authors.forename: Siyun
authors.initials: S
authors.lastname: Xu
authors.forename: Lushan
authors.initials: L
authors.lastname: Yu
authors.forename: Huidi
authors.initials: H
authors.lastname: Jiang
authors.forename: Su
authors.initials: S
authors.lastname: Zeng
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001060:Aporphines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D001060:Aporphines; C030168:isocorydine