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Planta Med 2012; 78(3): 252-259
DOI: 10.1055/s-0031-1280384
Pharmacokinetic Investigations
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Quantitative Determination of Decursin, Decursinol Angelate, and Decursinol in Mouse Plasma and Tumor Tissue Using Liquid-Liquid Extraction and HPLC

Li Li1 , 4 , Jinhui Zhang1 , 4 , Ahmad Ali Shaik1 , 2 , Yong Zhang1 , 4 , Lei Wang1 , Chengguo Xing2 , Sung-Hoon Kim1 , 3 , Junxuan Lü1 , 4
  • 1The Hormel Institute, University of Minnesota, Austin, Minnesota, USA
  • 2Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota, USA
  • 3Cancer Preventive Material Development Research Center and Institute, College of Oriental Medicine, Kyunghee University, Seoul, Republic of Korea
  • 4Current address: Department of Biomedical Sciences, Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo, Texas, USA
Further Information

Publication History

received June 22, 2011 revised Nov. 1, 2011

accepted Nov. 6, 2011

Publication Date:
24 November 2011 (online)

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Abstract

The pyranocoumarin compound decursin and its isomer decursinol angelate (DA) are the major hydrophobic phytochemicals in the root of Angelica gigas Nakai (AGN, Korean Angelica), a major traditional medicinal herb. The ethanol extract of AGN and especially the purified decursin and DA have been shown to exhibit antitumor activities by our collaborative team and others. Although decursinol has been identified as a major hydrolysis metabolite of decursin and DA in vivo in previous pharmacokinetic studies with mouse and rat, other recently published results sharply disputed this conclusion. In this study, we set up a practical method for the concurrent analysis of decursin, DA, and decursinol in mouse plasma and tumor tissues by liquid–liquid extraction and HPLC-UV and applied the method to several animal experiments. Plasma or tumor homogenate was extracted directly with ethyl acetate. The extraction efficiency for decursin/DA (quantitated together) and decursinol was between 82–95 % in both mouse plasma and tumor homogenate. The lower limit of quantitation (LLOQ) was approximately 0.25 µg/mL for decursin/DA and 0.2 µg/mL for decursinol in mouse plasma. In a pilot pharmacokinetic study, male C57BL/6 mice were given a single dose of 4.8 mg decursin/DA mixture (∼ 240 mg/kg) per mouse either by oral gavage or intraperitoneal injection. Maximum plasma concentrations for decursin/DA and decursinol were 11.2 and 79.7 µg/mL, respectively, when decursin/DA was administered via intraperitoneal injection, and 0.54 and 14.9 µg/mL via oral gavage. Decursin/DA and decursinol contents in the tumor tissues from nude mouse xenografts correlated very well with those in plasma. Overall, our results confirm the conclusion that the majority of decursin/DA hydrolyze to decursinol in rodent models with a tiny fraction remaining as the intact compounds administered.

Key words

decursin/decursinol angelate - decursinol - HPLC - mouse plasma - tumor tissue - Angelica gigas - Apiaceae

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Dr. Junxuan Lü

Department of Biomedical Sciences
Texas Tech University Health Sciences Center, School of Pharmacy

1300 S. Coulter St

Amarillo, TX 79106

USA

Phone: +1 80 63 56 40 15 ext. 250

Fax: +1 80 63 56 46 43

Email: junxuan.lu@ttuhsc.edu

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