title: A novel GC-MS method for determination of chrysophanol in rat plasma and tissues: Application to the pharmacokinetics, tissue distribution and plasma protein binding studies.
abstract: The purpose of this study was to explore the plasma protein binding (PPB), pharmacokinetics profiles and tissue distribution of chrysophanol in rats. Biological samples were extracted by ethyl ether, separated and determined by a novel, sensitive and specific GC-MS method under selected ion monitoring (SIM) mode for the first time. This method was validated for the quantification of chrysophanol, in the range of 0.005-1.50μgmL-1in rat plasma and 0.04-12μgmL-1in tissue homogenates, respectively. The limit of detection (LOD) was 0.4ngmL-1or 5.0ngg-1, which obtained excellent sensitivity for the pharmacokinetics analysis in rats. The intra- and inter-day assay of precisions in plasma and tissues were less than 10% and the intra- and inter-day accuracies were 82.1-92.9%. The method recoveries of all samples were more than 90%, except for liver samples (>80%), which indicated that chrysophanol may be partly metabolized in liver homogenates. The PPB rates in rat plasma, human plasma and bovine serum albumin were 83±2, 88±3 and 58±3%, respectively. The main pharmacokinetic parameters were the time of peak concentration (Tmax)=(0.665±0.034) h, the peak concentration (Cmax)=(929.8±102.7)ngmL-1, the area under the curve (AUC)=(1197.6±258.5)nghmL-1and the clearance (CL)=(0.013±0.0028)mLmg-1h-1. The tissue distribution of chrysophanol in rats after the oral administration showed a decreasing tendency in different tissues (heart>kidney>spleen>liver>lung>cerebrum).
authors.affiliation: Affiliated Dongfeng Hospital, Hubei University of Medicine, Hubei 442008, China; College of Pharmacy, University of Illinois at Chicago, IL 60612, USA. Electronic address: cqh77@163.com.
authors.forename: Qinhua
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Affiliated Dongfeng Hospital, Hubei University of Medicine, Hubei 442008, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: He
authors.affiliation: College of Pharmacy, University of Illinois at Chicago, IL 60612, USA.
authors.forename: Shangwen
authors.initials: S
authors.lastname: Luo
authors.affiliation: Affiliated Dongfeng Hospital, Hubei University of Medicine, Hubei 442008, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Affiliated Dongfeng Hospital, Hubei University of Medicine, Hubei 442008, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
keywords: Chrysophanol; GC/MS; Pharmacokinetics; Plasma protein binding; Tissue distribution