Planta Med 2013; 79(14): 1324-1328
DOI: 10.1055/s-0033-1350675
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

An UFLC–MS/MS Method for Quantification of Panaxadiol in Rat Plasma and Its Application to a Pharmacokinetic Study

Cai Xiaojun
1   School of Pharmaceutical Sciences, Wenzhou Medical College, Wenzhou, China
,
Xu Yuping
1   School of Pharmaceutical Sciences, Wenzhou Medical College, Wenzhou, China
,
Pan Yu
1   School of Pharmaceutical Sciences, Wenzhou Medical College, Wenzhou, China
,
Ren Yiping
2   Zhejiang Provincial Center for Disease Prevention and Control, Hangzhou, China
,
Xiang Zheng
1   School of Pharmaceutical Sciences, Wenzhou Medical College, Wenzhou, China
› Author Affiliations
Further Information

Publication History

received 13 March 2013
revised 03 June 2013

accepted 29 June 2013

Publication Date:
07 August 2013 (online)

Abstract

Panaxadiol is a novel antitumor agent extracted from the Chinese medical herb Panax ginseng. This agent is being developed for the treatment of tumor diseases. A rapid, selective, and simple method based on ultrafast liquid chromatography-tandem mass spectrometry was established and validated to determine panaxadiol in rat plasma following oral and sublingual intravenous administration of panaxadiol. The plasma samples were pretreated with acetic ether, and chromatographic separation was achieved on a Shim-pack XR-ODS III column using isocratic elution with the mobile phase of 0.1 % formic acid and acetonitrile. Analytes and protopanaxadiol (internal standard) were analyzed and identified using electrospray positive ionization mass spectrometry in the multiple reaction-monitoring mode. The MS/MS detection was carried out by monitoring the fragmentation of m/z 461.45 → m/z 127.1 for panaxadiol and m/z 425.4 → m/z 95.1 for protopanaxadiol (internal standard) on a triple-quadrupole mass spectrometer. The result showed good linearity over a wide concentration range (0.1–20 ng/mL) (R2 > 0.999) and its lower limit of detection and quantification were 0.03 and 0.1 ng/mL, respectively. The intra- and interday precision (RSD %) was within 15 % and the accuracy ranged from 94.9 % to 112.0 %. The absolute bioavailability was 12.5 %. The method was fully validated and successfully applied to the pharmacokinetic study of a single dose of panaxadiol.

 
  • References

  • 1 Li BH, Wang CZ, He TC, Yuan CS, Du W. Antioxidants potentiate American ginseng-induced killing of colorectal cancer cells. Cancer Lett 2010; 289: 62-70
  • 2 Bao PP, Lu W, Cui Y, Zheng Y, Gu K, Chen Z, Zheng W, Shu XO. Ginseng and Ganoderma lucidum use after breast cancer diagnosis and quality of life: a report from the Shanghai Breast Cancer Survival Study. PLoS One 2012; 7: e39343
  • 3 Kim JH. Cardiovascular diseases and Panax ginseng: a review on molecular mechanisms and medical applications. J Ginseng Res 2012; 36: 16-26
  • 4 Jia YL, Zhang SK, Huang FY, Leung SW. Could ginseng-based medicines be better than nitrates in treating ischemic heart disease? A systematic review and meta-analysis of randomized controlled trials. Complement Ther Med 2012; 20: 155-166
  • 5 Hur MH, Lee MS, Yang HJ, Kim C, Bae IL, Ernst E. Ginseng for reducing the blood pressure in patients with hypertension: a systematic review and meta-analysis. J Ginseng Res 2010; 34: 342-347
  • 6 Kim DY, Yang WM. Panax ginseng ameliorates airway inflammation in an ovalbumin-sensitized mouse allergic asthma model. J Ethnopharmacol 2011; 136: 230-235
  • 7 Xie XS, Liu HC, Yang M, Zuo C, Deng Y, Fan JM. Ginsenoside Rb1, a panoxadiol saponin against oxidative damage and renal interstitial fibrosis in rats with unilateral ureteral obstruction. Chin J Integr Med 2009; 15: 133-140
  • 8 Wang ZH, Zheng QS, Liu K, Li G, Zheng R. Ginsenoside Rh-2 enhances antitumour activity and decreases genotoxic effect of cyclophosphamide. Basic Clin Pharmacol 2006; 98: 411-415
  • 9 Zeng QH, Liu J. Protective effect of ginseng panaxadiol monor Rb1 on assay the index of biochemistry of myocardial ischaemia of rat. FASEB J 2004; 18: A1090-A1090
  • 10 Zeng QH, Liu J. Study of protective effect of ginseng panaxadiol on assay the index of biochemistry of myocardial ischaemia. FASEB J 2006; 20: A1288-A1288
  • 11 Ren HC, Sun JG, Wang GJ, A JY. Xie HT, Zha WB, Yan B, Sun FZ, Hao HP, Gu SH, Sheng LS, Shao F, Shi J, Zhou F. Sensitive determination of 20(S)-protopanaxadiol in rat plasma using HPLC-APCI-MS: application of pharmacokinetic study in rats. J Pharm Biomed Anal 2008; 48: 1476-1480
  • 12 Zhao J, Su C, Yang CP, Liu MH, Tang L, Su WW, Liu ZQ. Determination of ginsenosides Rb-1, Rb-2, and Rb-3 in rat plasma by a rapid and sensitive liquid chromatography tandem mass spectrometry method: Application in a pharmacokinetic study. J Pharm Biomed Anal 2012; 64–65: 94-97
  • 13 Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs 2009; 69: 1777-1798
  • 14 Qi LW, Wang CZ, Du GJ, Zhang ZY, Calway T, Yuan CS. Metabolism of ginseng and its interactions with drugs. Curr Drug Metab 2011; 12: 818-822
  • 15 Joo KM, Lee JH, Jeon HY, Park CW, Hong DK, Jeong HJ, Lee SJ, Lee SY, Lim KM. Pharmacokinetic study of ginsenoside Re with pure ginsenoside Re and ginseng berry extracts in mouse using ultra performance liquid chromatography/mass spectrometric method. J Pharm Biomed 2010; 51: 278-283