title: Simultaneous determination of ten alkaloids of crude and wine-processed Rhizoma Coptidis aqueous extracts in rat plasma by UHPLC-ESI-MS/MS and its application to a comparative pharmacokinetic study.
abstract: Rhizoma coptidis (R.C.), a widely used traditional Chinese medicine, has been used for centuries in the treatment of hypertension, inflammation, dysentery and liver diseases, etc. Wine-processing is a specialized technology by sautéing crude herbal medicine using Chinese rice wine. This paper was designed to establish a simultaneous quantitative method of ten alkaloids (berberine, coptisine, palmatine, jatrorrhizine, epiberberine, magnoflorine, columbamine, noroxyhydrastinine, oxyberberine and 8-oxocoptisine) in rat plasma. Furthermore, the pharmacokinetics of those alkaloids after administration of crude and wine-processed R.C. aqueous extracts was compared. As a result, a ultra high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) method was developed and validated for the first time. Chromatographic separation was achieved on a C18 column using gradient elution with the mobile phase consisting of acetonitrile and water (containing 0.2% formic acid) at a flow rate of 0.2 ml/min. The validated method showed good linearity over a wide concentration range (r>0.99), and lower limits of quantification less than 5.46 ng/ml for the each analyte. The intra- and inter-day assay variability was below 9.9% and 10.5% for all analytes, respectively. The extraction recovery of those alkaloids and I.S. ranged from 65.3% to 90.7%. The validated method has been successfully applied to pharmacokinetic comparison after administration of crude and wine-processed R.C. aqueous extracts. Pharmacokinetic comparative study showed that Cmax of coptisine and 8-oxocoptisine and AUC0-t of coptisine, palmatine and 8-oxocoptisine were increased significantly (p<0.05) after wine-processing, while other compounds didn't show significant difference, which suggested that wine-processing exerted limited effects on the absorption of alkaloids. These results might be helpful for R.C.' clinical reasonable application and further studies on its wine-processing mechanism.
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System (DDS), Nanjing 210023, China.
authors.forename: Xiao-Cui
authors.initials: XC
authors.lastname: Qian
authors.affiliation: Key Laboratory of Tea Biochemistry & Biotechnology, Ministry of Education and Ministry of Agriculture, Anhui Agricultural University, Hefei 230036, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tao
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System (DDS), Nanjing 210023, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Huang
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System (DDS), Nanjing 210023, China. Electronic address: lijunsong1964@163.com.
authors.forename: Jun-Song
authors.initials: JS
authors.lastname: Li
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Chai
authors.affiliation: Nanjing Municipal Hospital of Traditional Chinese Medicine, Nanjing 210001, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System (DDS), Nanjing 210023, China.
authors.forename: Liu-Qing
authors.initials: LQ
authors.lastname: Di
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Bao-Chang
authors.initials: BC
authors.lastname: Cai
mesh_terms: D000470:Alkaloids / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D039323:Coptis / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D008297:Male; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D027343:Rhizome / Q000737:chemistry; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014867:Water / Q000737:chemistry; D014920:Wine
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal; D014867:Water
keywords: Alkaloids; Pharmacokinetics; Rhizoma coptidis; Rice wine processing; UHPLC–MS/MS