title: Pharmacokinetics in rats and tissue distribution in mouse of magnoflorine by ultra performance liquid chromatography-tandem mass spectrometry.
abstract: Magnoflorine is one of the most widespread aporphine alkaloids. In this work, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of magnoflorine in rat plasma and mouse tissue have been developed and validated. After addition of nuciferine as an internal standard (IS), protein precipitation by acetonitrile-methanol (9:1, v/v) was used for samples treatment. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 mm×100 mm, 1.7 μm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 342.8→298.2 for magnoflorine and m/z 296.0→265.1 for IS. Calibration plots were linear throughout the range 2-2000 ng/mL for magnoflorine in rat plasma and tissue. Mean recoveries of magnoflorine in rat plasma were better than 83.0%. RSD of intra-day and inter-day precision were both less than 9%. The accuracy of the method was between 95.5% and 107.5%. The method was successfully applied to pharmacokinetics and tissue distribution study of magnoflorine. The absolute bioavailability of magnoflorine was reported as 22.6%. The magnoflorine underwent a rapid and wide distribution to tissues; the level of magnoflorine in liver is highest, then followed by heart, spleen and lung. Based on tissue distribution data, a back-propagation artificial neural network (BP-ANN) method was developed and it could be used to predict the concentrations of magnoflorine in tissues.
authors.affiliation: The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325000, China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Bao
authors.affiliation: The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui Lishui 323000, China.
authors.forename: Peiwu
authors.initials: P
authors.lastname: Geng
authors.affiliation: The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui Lishui 323000, China.
authors.forename: Shuanghu
authors.initials: S
authors.lastname: Wang
authors.affiliation: The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui Lishui 323000, China.
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325035, China.
authors.forename: Lufeng
authors.initials: L
authors.lastname: Hu
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325035, China.
authors.forename: Xuezhi
authors.initials: X
authors.lastname: Yang
keywords: Magnoflorine; UPLC-MS/MS; pharmacokinetics; rat; tissue distribution