title: Highly sensitive method for simultaneous determination of nine alkaloids of Shuanghua Baihe tablets in human plasma by LC-MS/MS and its application.
abstract: Shuanghua Baihe tablets (SBT) is a traditional Chinese medicinal formula which has been used to treat recurrent aphthous stomatitis for many years. To study the pharmacokinetic profiles of berberine, epiberberine, coptisine, palmatine, jatrorrhizine, magnoflorine, berberrubine, corynoline and acetylcorynoline in human after administration of SBT, a sensitive liquid chromatography-tandem mass spectrometry method was developed and fully validated for the simultaneous quantification of these nine alkaloids in human plasma. After protein precipitation, the nine alkaloids in human plasma sample was separated on a Hanbon C18 (150mm×2.1mm, 5μm) column with gradient elution using methanol and 0.5% formic acid water solution, and detected by a triple quadrupole mass spectrometer with an electrospray ionization source. It is a challenge to design different calibration ranges for different analytes in a bioanalytical method for simultaneous determination of multi-analytes in bio-samples. To ensure that each alkaloid in the plasma was determined accurately by the simultaneous quantitation method, the upper limits of quantification for the nine alkaloids were designed at 100, 300, 800, 1800 and 5000pg/mL, respectively, according to the maximum plasma concentration value of each alkaloid obtained from the pilot pharmacokinetic study. The lower limit of quantification was 15pg/mL for berberine, epiberberine, coptisine, magnoflorine, berberrubine, corynoline and acetylcorynoline, while for palmatine and jatrorrhizine it was 1.5pg/mL. This method was successfully applied to investigate the pharmacokinetic profiles of the nine alkaloids in healthy Chinese volunteers after a single oral administration of SBT.
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Nanjing Clinical Tech Laboratories Inc., 18 Zhilan Road, Jiangning District, Nanjing 211000, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Nanjing Clinical Tech Laboratories Inc., 18 Zhilan Road, Jiangning District, Nanjing 211000, PR China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Nanjing Clinical Tech Laboratories Inc., 18 Zhilan Road, Jiangning District, Nanjing 211000, PR China.
authors.forename: Pan
authors.initials: P
authors.lastname: Gu
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Nanjing Clinical Tech Laboratories Inc., 18 Zhilan Road, Jiangning District, Nanjing 211000, PR China.
authors.forename: Minlu
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Yangtze River Pharmaceutical Group, Taizhou 225321, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Yangtze River Pharmaceutical Group, Taizhou 225321, PR China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, 12 Jiangwangmiao Street, Nanjing 210042, PR China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Ma
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Nanjing Clinical Tech Laboratories Inc., 18 Zhilan Road, Jiangning District, Nanjing 211000, PR China. Electronic address: dinglidl@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
mesh_terms: D000470:Alkaloids / Q000097:blood*; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000032:analysis*; D006801:Humans; D057230:Limit of Detection; D012015:Reference Standards; D015203:Reproducibility of Results; D013607:Tablets; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal; D013607:Tablets
keywords: Berberine; Coptisine; Corynoline; LC–MS/MS; Palmatine; Shuanghua Baihe tablets