title: Simultaneous determination of seven alkaloids in rat plasma by UFLC-MS/MS and its application to a pharmacokinetic study after oral administration of Cerebralcare Granule.
abstract: An ultra fast liquid chromatography-tandem mass sepectrometry (UFLC-MS/MS) method was developed for simultaneous determination of seven active alkaloid components (tetrahydropalmatine, corydaline, α-allocryptopine, tetrahydroberberine, tetrahydrocoptisine, tetrahydrocolumbamine and dehydrocorydaline) in rat plasma after oral administration of Cerebralcare Granule. Plasma samples were pretreated by protein precipitation with acetronitrile containing the internal standard diazepam. Chromatographic separation was achieved on a Phenomenex Kinetex C18 column (100×2.1mm, 2.6μm) with gradient elution using mobile phase consisting of acetonitrile -0.1% formic acid in water at a flow rate of 0.3mL/min. The detection was performed on an electrospray ionization triple quadrupole tandem mass spectrometer using multiple reaction monitoring (MRM) with positive ionization mode. The established method was fully validated and proved to be sensitive and specific with lower limits of quantification (LLOQs) all less than 0.0265ng/mL in rat plasma. Good linearities of seven alkaloids were obtained in respective concentration ranges (r>0.9923). The intra- and inter-day precisions were below of 15% for all the seven alkaloids in terms of relative standard deviation (RSD), and the accuracies were ranged from -2.7% to 8.3% in terms of relative error (RE). Extraction recovery, matrix effect and stability were within the required limits in rat plasma. The validated method was successfully applied to investigate the pharmacokinetics of the seven alkaloids in rat plasma after oral administration of Cerebralcare Granule (CG).
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xiaowen
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Tianjin 300402, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Ling
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Tianjin 300402, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yunfei
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China. Electronic address: sgxwm0416@163.com.
authors.forename: Sun
authors.initials: S
authors.lastname: Guoxiang
authors.affiliation: China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Dailin
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Tianjin 300402, China.
authors.forename: Sun
authors.initials: S
authors.lastname: Herry
mesh_terms: D000284:Administration, Oral; D000470:Alkaloids / Q000097:blood*; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics*; D057230:Limit of Detection; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal; C553222:cerebralcare preparation
keywords: Alkaloids; Cerebralcare Granule; Pharmacokinetics; UFLC-MS/MS