title: Development of a sensitive and rapid UPLC-MS/MS method for the determination of koumine in rat plasma: application to a pharmacokinetic study.
abstract: A rapid, selective and sensitive method using UPLC-MS/MS was first developed and validated for quantitative analysis of koumine in rat plasma. A one-step protein precipitation with methanol was employed as a sample preparation technique. Plasma samples were separated on an Acquity UPLC BEH C18 column (50 × 2.1 mm, i.d. 1.7 µm) with a gradient mobile phase consisting of methanol with 0.1% (v/v) formic acid and water containing 0.1% (v/v) formic acid at a flow rate of 0.3 mL/min. Detection and quantification were performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode via positive eletrospray ionization. Good linearity (r > 0.9997) was achieved using weighted (1/x(2) ) least squares linear regression over a concentration range of 0.025-15 µg/mL with a lower limit of quantification of 0.025 µg/mL for koumine. The intra- and inter- precisions (relative standard deviation) of the assay at all three quality control samples were 5.6-14.1% with an accuracy (relative error) of 5.0-14.0%, which meets the requirements of the US Food and Drug Administration guidance. This developed method was successfully applied to an in vivo pharmacokinetic study in rats after a single intravenous dose of 20 mg/kg koumine.
authors.affiliation: School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, China. chenjz1977@126.com
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Xiao
authors.forename: Shui-Sheng
authors.initials: SS
authors.lastname: Wu
authors.forename: Heng-Wen
authors.initials: HW
authors.lastname: Song
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005260:Female; D026121:Indole Alkaloids / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D016018:Least-Squares Analysis; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D026121:Indole Alkaloids; C515085:koumine