title: Simultaneous quantification and semi-quantification of ginkgolic acids and their metabolites in rat plasma by UHPLC-LTQ-Orbitrap-MS and its application to pharmacokinetics study.
abstract: A highly sensitive method using ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS) has been developed and validated for the simultaneous identification and quantification of ginkgolic acids and semi-quantification of their metabolites in rat plasma. For the five selected ginkgolic acids, the method was found to be with good linearities (r>0.9991), good intra- and inter-day precisions (RSD<15%), and good accuracies (RE, from -10.33% to 4.92%) as well. Extraction recoveries, matrix effects and stabilities for rat plasm samples were within the required limits. The validated method was successfully applied to investigate the pharmacokinetics of the five ginkgolic acids in rat plasma after oral administration of 3 dosage groups (900mg/kg, 300mg/kg and 100mg/kg). Meanwhile, six metabolites of GA (15:1) and GA (17:1) were identified by comparison of MS data with reported values. The results of validation in terms of linear ranges, precisions and stabilities were established for semi-quantification of metabolites. The curves of relative changes of these metabolites during the metabolic process were constructed by plotting the peak area ratios of metabolites to salicylic acid (internal standard, IS), respectively. Double peaks were observed in all 3 dose groups. Different type of metabolites and different dosage of each metabolite both resulted in different Tmax.
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resource Industrializ-ation, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, China.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resource Industrializ-ation, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resource Industrializ-ation, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, China. Electronic address: dja@njutcm.edu.cn.
authors.forename: Jin-Ao
authors.initials: JA
authors.lastname: Duan
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resource Industrializ-ation, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Guo
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resource Industrializ-ation, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, China.
authors.forename: Erxin
authors.initials: E
authors.lastname: Shang
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resource Industrializ-ation, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, China; School of Pharmacy, Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Tao
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resource Industrializ-ation, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, China.
authors.forename: Shulan
authors.initials: S
authors.lastname: Su
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resource Industrializ-ation, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Guo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D057230:Limit of Detection; D016014:Linear Models; D013058:Mass Spectrometry / Q000379:methods*; D051381:Rats; D015203:Reproducibility of Results; D012459:Salicylates / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D012459:Salicylates; C112485:ginkgolic acid
keywords: Ginkgolic acids; Metabolites; Pharmacokinetics; UHPLC–LTQ–Orbitrap–MS