title: Determination of N-methylcytisine in rat plasma by UPLC-MS/MS and its application to pharmacokinetic study.
abstract: In this work, a sensitive and selective UPLC-MS/MS method for determination of N-methylcytisine in rat plasma is developed. After addition of hordenine as an internal standard (IS), protein precipitation by acetonitrile-methanol (9:1, v/v) was used to prepare samples. Chromatographic separation was achieved on a UPLC BEH HILIC (2.1 mm×100mm, 1.7μm) with acetonitrile (containing 10mM ammonium formate) and water (containing 0.1% formic acid and 10mM ammonium formate) as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) mode was used for quantification using target fragment ions m/z 205.1→58.0 for N-methylcytisine, and m/z 166.1→121.0 for IS. Calibration plots were linear throughout the range 2-2000ng/mL for N-methylcytisine in rat plasma. Mean recoveries of N-methylcytisine in rat plasma ranged from 86.1% to 94.8%. RSD of intra-day and inter-day precision were both<13%. The accuracy of the method was between 94.5% and 109.4%. The method was successfully applied to pharmacokinetic study of N-methylcytisine after either oral or intravenous administration. For the first time, the absolute bioavailability of N-methylcytisine was reported as high as 55.5%.
authors: The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui, Wenzhou Medical University, Lishui 323000, China.
authors: Shuanghu
authors: S
authors: Wang
authors: Department of Anesthesiology, Critical Care and Pain Medicine, the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China.
authors: Haiya
authors: H
authors: Wu
authors: Analytical and Testing Center, Wenzhou Medical University, Wenzhou 325035, China.
authors: Xueli
authors: X
authors: Huang
authors: The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui, Wenzhou Medical University, Lishui 323000, China.
authors: Peiwu
authors: P
authors: Geng
authors: Analytical and Testing Center, Wenzhou Medical University, Wenzhou 325035, China.
authors: Congcong
authors: C
authors: Wen
authors: Analytical and Testing Center, Wenzhou Medical University, Wenzhou 325035, China.
authors: Jianshe
authors: J
authors: Ma
authors: The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui, Wenzhou Medical University, Lishui 323000, China. Electronic address: zyf2808@126.com.
authors: Yunfang
authors: Y
authors: Zhou
authors: Analytical and Testing Center, Wenzhou Medical University, Wenzhou 325035, China. Electronic address: lankywang@163.com.
authors: Xianqin
authors: X
authors: Wang
mesh_terms: D000470:Alkaloids / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D011807:Quinolizines / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000093843:Quinolizidine Alkaloids
chemical_list: D000470:Alkaloids; D011807:Quinolizines; C034245:N-methylcytisine; D000093843:Quinolizidine Alkaloids
keywords: N-methylcytisine; UPLC-MS/MS; pharmacokinetics; rat plasma