title: Simultaneous determination of six alkaloid components in rat plasma and its application to pharmacokinetic study of Danmu preparations by an ultra fast liquid chromatography-electrospray ionization-tandem mass spectrometry.
abstract: Danmu injection and Danmu tablet are two widely used traditional Chinese medicine made of Nauclea officinalis (commonly known as Danmu), in which the alkaloids are the major active substances. In this paper, an ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method was developed for simultaneous determination and the pharmacokinetic characteristics study of six main active alkaloids (naucleamide A-10-O-β-d-glucopyranosid, naucleamide G, pumiloside, 3-epi-pumiloside, strictosamide and vincosamide) of the two above-mentioned Danmu preparations in rat plasma. In the course of the experiment, following sample preparation by protein precipitation with methanol-ethyl acetate (2:1, v/v), the nitrogen-dried extraction was reconstituted in methanol and assayed on a C18 column using a gradient elution program with mobile phase consisting of acetonitrile and water containing 0.1% formic acid. The MS detection was performed in positive ionization mode with selected ion transitions. The established method was fully validated and proved to be sensitive and specific with lower limits of quantification (LLOQs) all less than 0.32ng/mL in rat plasma and matrix effects ranged from 88.87 to 108.27%. Good linearities of six alkaloids were obtained in respective concentration ranges (r(2)>0.995). The average extract recoveries for each compound at three quality control concentration levels were no less than 79.70%, and the precision and accuracy were within the acceptable limits. The validated method was successfully applied to the pharmacokinetic study of six alkaloid components of Danmu injection and tablet in rat plasma. The obtained results may be helpful to reveal the action mechanism and guide the clinical application of Danmu preparations.
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing 210028, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yin
authors.affiliation: Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jiaquan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Jiangsu Environmental Monitoring Center, Nanjing 210036, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing 210028, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Jia
authors.affiliation: College of Pharmacy, Hainan Medical University, Haikou 570102, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing 210028, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing 210028, China; Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing 210028, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing 210028, China. Electronic address: sunshinezhu@yeah.net.
authors.forename: Fenxia
authors.initials: F
authors.lastname: Zhu
mesh_terms: D000470:Alkaloids / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal; C000602095:danmu
keywords: Alkaloid components; Danmu injection; Danmu tablet; Pharmacokinetic study; UFLC–MS/MS