title: A sensitive method for determination of platycodin d in rat plasma using liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study.
abstract: Platycodin D (PD), a major component isolated from the root of Platycodon grandiflorum, is widely used in traditional Chinese medicine. A sensitive rapid analytical method was established and validated to determine the PD in rat plasma. This method was further applied to assess the pharmacokinetics of PD in rats following administration of a single dose. Liquid chromatography tandem mass spectrometry (LC/MS/MS) in multiple reaction monitoring mode (MRM) was used in the method, and tubeimoside I was used as the internal standard (IS). A simple protein precipitation based on methanol (MeOH) was employed. The combination of a simple sample cleanup and short chromatographic running time (4 min) increased the throughput of the method substantially. The method was validated over the range of 0.5-1000 ng/mL with a correlation coefficient > 0.99. The lower limit of quantification was 0.5 ng/mL for PD in plasma. Intra- and inter-day accuracies for PD were 90-115 % and 96-108 %, respectively, and the inter-day precision was less than 15 %. After a single oral dose of 10 mg/kg of PD, its mean peak plasma concentration ( CMAX) was 13.7 ± 4.5 ng/mL at 0.5 h. The area under the plasma concentration-time curve ( AUC0-24 H) was 35.4 ± 16.1 h·ng/mL, and the elimination half-life ( T1/2) was 1.48 ± 0.13 h. In case of intravenous administration of PD at a dosage of 0.5 mg/kg, the area under the plasma concentration-time curve ( AUC0-24 H) was 2203 ± 258 h · ng/mL, and the elimination half-life (T½) was 6.57 ± 0.70 h. Based on the results, the oral bioavailability of PD in rats at 10 mg/kg is 0.079 %.
authors.affiliation: Pharmacology Laboratory of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Pei
authors.forename: Yuanwu
authors.initials: Y
authors.lastname: Bao
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.forename: Qiqi
authors.initials: Q
authors.lastname: Wang
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Ye
authors.forename: Xianghui
authors.initials: X
authors.lastname: Han
authors.forename: Sheng
authors.initials: S
authors.lastname: Liu
authors.forename: Xiuping
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D008297:Male; D010936:Plant Extracts / Q000097:blood / Q000493:pharmacokinetics; D031238:Platycodon / Q000737:chemistry; D051381:Rats; D012503:Saponins / Q000097:blood* / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods; D014315:Triterpenes / Q000097:blood* / Q000493:pharmacokinetics*
chemical_list: D010936:Plant Extracts; D012503:Saponins; D014315:Triterpenes; C051084:tubeimoside I; C108953:platycodin D