title: Quantitative determination of diterpenoid alkaloid Fuziline by hydrophilic interaction liquid chromatography (HILIC)-electrospray ionization mass spectrometry and its application to pharmacokinetic study in rats.
abstract: A rapid, sensitive and specific hydrophilic interaction liquid chromatography coupled to electrospray ionization mass spectrometric (HILIC-MS) method for the quantification of Fuziline (15α-Hydroxyneoline) in rat plasma was developed and validated. After liquid-liquid extraction with ethyl acetate, Fuziline and Guanfu base A (internal standard) were separated with HILIC Chrom Matrix HP amide column (5μm, 10cm×3.0mm I.D.) with isocratic elution at a flow-rate of 0.2mL/min. The analytes were detected by using an electrospray positive ionization mass spectrometry in the selected ion monitoring (SIM) mode. A good linear relationship was obtained in the concentration ranging from 1 to 1000ng/mL (R(2)=0.999) with the lower limit of quantification (LLOQ) at 1ng/mL and limit of detection (LOD) at 0.5ng/mL. The average recoveries of Fuziline in plasma at the concentrations of 2, 50, 1000ng/mL ranged from 68.2 to 69.9%. Intra- and inter-batch relative standard deviations ranged from 1.5 to 3.3% and 2.6 to 8.3%, respectively. Fuziline was stable under different sample storage and processing conditions except three-cycle freeze-thaw treatment at 2ng/mL. This method was successfully applied to the pharmacokinetic studies in Sprague-Dawley rats. The absolute bioavailability of Fuziline after oral administration 4mg/kg Fuziline in rats was 21.1±7.0%, with clearance rate at 1745.6±818.1mL/kg/h, and half-life at about 6.3±2.6h.
authors.affiliation: Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Sun
authors.forename: Fengyi
authors.initials: F
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.forename: Jinghan
authors.initials: J
authors.lastname: Liu
authors.forename: Yunxi
authors.initials: Y
authors.lastname: Zhong
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
mesh_terms: D031841:Aconitum / Q000737:chemistry; D000470:Alkaloids / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004224:Diterpenes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D005260:Female; D057927:Hydrophobic and Hydrophilic Interactions; D057230:Limit of Detection; D059625:Liquid-Liquid Extraction; D008297:Male; D010936:Plant Extracts / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000470:Alkaloids; D004224:Diterpenes; D010936:Plant Extracts