title: Simultaneous determination of ten Aconitum alkaloids in rat tissues by UHPLC-MS/MS and its application to a tissue distribution study on the compatibility of Heishunpian and Fritillariae thunbergii Bulbus.
abstract: A rapid, sensitive and selective ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for simultaneous determination of ten Aconitum alkaloids in rat tissues. The tissue samples were prepared by a simple procedure protein precipitation with acetonitrile containing 0.1% acetic acid and separated on an Agilent XDB C18 column (4.6 mm×50mm, 1.8μm) using gradient elution with a mobile phase consisting of water and acetonitrile (both containing 0.1% formic acid) at a flow rate of 0.3mL/min. The quantitive determination was performed on an electrospray ionization (ESI) triple quadrupole tandem mass spectrometer using selective reaction monitoring (SRM) under positive ionization mode. The established method was fully validated according to the USA Food and Drug Administration (FDA) bioanalytical method validation guidance and the results demonstrated that the method was sensitive and selective with the lowest limits of quantification (LLOQ) at 0.025ng/mL in rat tissue homogenates. Meanwhile, the linearity, precision, accuracy, extraction recovery, matrix effect and stability were all within the required limits of biological sample analysis. After method validation, the validated method was successfully applied to the tissue distribution study on the compatibility of Heishunpian (HSP, the processed product of Aconitum carmichaelii Debx) and Fritillariae thunbergii Bulbus (Zhebeimu, ZBM). The results indicated that the distribution feature of monoester diterpenoid aconitines (MDAs), diester diterpenoid aconitines (DDAs) and non-ester alkaloids (NEAs) were inconsistency, and the compatibility of HSP and ZBM resulted in the distribution amount of DDAs increased in tissues. What's more, the results could provide the reliable basis for systematic research on the substance foundation of the compatibility of the herbal pair.
authors: College of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors: Bin
authors: B
authors: Yang
authors: College of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors: Yanyan
authors: Y
authors: Xu
authors: College of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors: Yuanyuan
authors: Y
authors: Wu
authors: First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 314 Anshan West Road, Tianjin 300193, China.
authors: Huanyu
authors: H
authors: Wu
authors: College of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors: Yuan
authors: Y
authors: Wang
authors: College of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors: Lei
authors: L
authors: Yuan
authors: College of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors: Jiabin
authors: J
authors: Xie
authors: College of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors: Yubo
authors: Y
authors: Li
authors: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China. Electronic address: tianjin_tcm001@sina.com.
authors: Yanjun
authors: Y
authors: Zhang
mesh_terms: D031841:Aconitum / Q000737:chemistry*; D000470:Alkaloids / Q000032:analysis* / Q000737:chemistry; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D057230:Limit of Detection; D008297:Male; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal; C000614235:heishunpian; C000614236:zhebeimu
keywords: Aconitum alkaloids; Heishunpian; Tissue distribution; UHPLC–MS/MS