title: Comparative pharmacokinetic studies of andrographolide and its metabolite of 14-deoxy-12-hydroxy-andrographolide in rat by ultra-performance liquid chromatography-mass spectrometry.
abstract: Andrographolide (AND), one of the major diterpenoids from Andrographis paniculata (Burm. f.) Nees, can be metabolized as a phase two metabolite of 14-deoxy-12-hydroxy-andrographolide-19-O-β-d-glucuronide in human. The aim of this study is to characterize and synthesize the phase one metabolite of 14-deoxy-12-hydroxy-andrographolide (DEO-AND) after gavage feeding of AND in rats, and to compare the pharmacokinetics of AND and DEO-AND after intravenous administration. DEO-AND was first discovered existing in rat serum by HPLC-MS(n) after administration of AND. Furthermore, the target metabolite was synthesized and elucidated by NMR. In addition, a rapid, selective and sensitive UPLC-ESI/MS method was developed for the first time to determine the content of AND and DEO-AND in rats serum. The method was successfully applied to a pharmacokinetic study in rats after a single intravenous dose of 5 mg/kg AND and DEO-AND, respectively. In comparison, the pharmacokinetic parameters of metabolite DEO-AND, including distribution rate constant, elimination rate constant, half-life and mean residence time, were significantly less than those of AND (p < 0.05). However, the AUC0→720 min value after intravenous administration of DEO-AND was 781.59 ± 81.46 µg min/mL, which was 17.71 times higher than that of AND (44.13 ± 10.45 µg min/mL; p < 0.05). These results show the pharmacokinetic profile of AND to be significantly different from that of DEO-AND by intravenous administration.
authors.affiliation: The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, The Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Zhangjiang Hi-Tech Park, Shanghai, 201210, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Chong
authors.initials: C
authors.lastname: Xu
authors.forename: Zheng Tao
authors.initials: ZT
authors.lastname: Wang
authors.forename: Chang Hong
authors.initials: CH
authors.lastname: Wang
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004224:Diterpenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016018:Least-Squares Analysis; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D004224:Diterpenes; C030419:andrographolide