Planta Med 2008; 74(15): 1832-1836
DOI: 10.1055/s-0028-1088339
Original Paper
Analytical Studies
© Georg Thieme Verlag KG Stuttgart · New York

Quantitative Determination of Ophiopogonin D by Liquid Chromatography/Electrospray Ionization Mass Spectrometry and its Pharmacokinetics in Rat

Chun-hua Xia1 , 2 , Jian-guo Sun1 , Hai-ping Hao1 , Guang-ji Wang1 , Bei Yan1 , Sheng-hua Gu1 , Chao-nan Zheng1 , Li-li Shang1 , Michael S. Roberts3
  • 1Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China
  • 2Clinical Pharmacology Institute, Medical College of Nanchang University, Nanchang, P. R. China
  • 3Therapeutics Research Unit, Southern Clinical Division, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia
Further Information

Publication History

Received: November 13, 2007 Revised: August 25, 2008

Accepted: August 28, 2008

Publication Date:
13 November 2008 (online)

Abstract

A sensitive and rapid liquid chromatography-mass spectrometric method for the determination of ophiopogonin D in rat plasma was developed and validated. Chromatographic separation was performed on a C18 column using a step gradient program with the mobile phase of 0.5 mmol/L ammonium chloride solution and acetonitrile. Ophiopogonin D was quantified using an electrospray negative ionization mass spectrometry in the selected ion monitoring (SIM) mode using digoxin as an internal standard. Good linearity was obtained in the concentration range of 2.5 – 480.0 ng/mL (r2 = 0.9984). The lower limit of quantification (LLOQ) and lower limit of detection (LLOD) were 2.5 ng/mL and 1.0 ng/mL, respectively. Both the intra- and inter-day precision was less than 8.9 % and the accuracy was within 97.5 – 107.3 %. The pharmacokinetic study of ophiopogonin D in rats was then defined using the method after intravenous dosing (77.0 μg/kg). The plasma concentration-time profile for ophiopogonin D was best fitted to an open two-compartment model with a clearance of 0.024 ± 0.010 L/min/kg and a terminal half life of 17.29 ± 1.70 min. A comparison of the pharmacokinetics of ophiopogonin D as a pure compound and as a component of ’SHENMAI’ injection revealed a significantly smaller clearance of ophiopogonin D (0.007 ± 0.002 L/min/kg) for the latter formulation, consistent with an inhibition by one or more other components in the formulation.

References

  • 1 Ji H Y, Lee H W, Kim H K, Kim H H, Chang S G, Sohn D H. et al . Simultaneous determination of ginsenoside Rb1 and Rg1 in human plasma by liquid chromatography-mass spectrometry.  J Pharm Biomed Anal. 2004;  35 207-12
  • 2 Li L, Zhang J L, Sheng Y X, Guo D A, Wang Q, Guo H Z. Simultaneous quantification of six major active saponins of Panax notoginseng by high-performance liquid chromatography-UV method.  J Pharm Biomed Anal. 2005;  38 45-51
  • 3 Sun J G, Wang G J, Xie H T, Li H, Pan G Y, Ian T. Simultaneous rapid quantification of ginsenoside Rg1 and its secondary glycoside Rh1 and aglycone protopanaxatriol in rat plasma by liquid chromatography-mass spectrometry after solid-phase extraction.  J Pharm Biomed Anal. 2005;  38 126-32
  • 4 Li X Y, Sun J G, Wang G J, Hao H P, Liang Y, Zheng Y T. et al . Simultaneous determination of Panax notoginsenoside R1, ginsenoside Rg1, Rd, Re and Rb1 in rat plasma by HPLC/ESI/MS: platform for the pharmacokinetic evaluation of total Panax notoginsenoside, a typical kind of multiple constituent traditional Chinese medicine.  Biomed Chromatogr. 2007;  21 735-46
  • 5 Yu K, Ma Y H, Shao Q, Qu H B, Cheng Y Y. Simultaneous determination of five ginsenosides in rabbit plasma using solid-phase extraction and HPLC/MS technique after intravenous administration of ’SHENMAI’ injection.  J Pharm Biomed Anal. 2007;  44 532-9
  • 6 Yu B Y, Xu G J, Hirai Y S, Shoji J Z. Simultaneous determination of glycoside B and glycoside J in the tuberous roots of Liriope spicata by HPLC.  J Chin Pharm Univ. 1991;  22 114-6
  • 7 Wu T, Yu B Y, Cheng Z H, Xu L S. Quantitative determination of the main saponin content in Hubei Liriope by HPLC-ELSD.  Chin Tradit Herb Drug. 2000;  31 175-7
  • 8 Yao L W, Wang G L, Wang F, Lin R C. Quantitative determination of ophiopogonin D' in Sichuan ophiopogon by HPLC-EL SD.  Chin Tradit Herb Drug. 2004;  35 1419-21
  • 9 Wu X R, Xu D S, Feng Y, Gu F. Quantitative determination of ophiopogonin D and ophiopogonin D' in Fibre ophiopogon enriched extract by macroporous resin.  Chin Tradit Pat Med. 2006;  28 1639-40
  • 10 Xu J T, Tang G P, Wu M. Quantitative determination of ophiopogonins by thin layer scanning.  J Pharm Anal. 1997;  17 164-6
  • 11 Ishibashi H, Mochidome T, Okai J, Ichiki H, Shimada H, Takahama K. Activation of potassium conductance by ophiopogonin-D in acutely dissociated rat paratracheal neurons.  . 2001;  132 461-6
  • 12 Kou J P, Sun Y, Lin Y W, Cheng Z H, Zheng W, Yu B Y. et al . Anti-inflammatory activities of aqueous extract from Radix Ophiopogon japonicus and its two constituents.  . 2005;  28 1234-8
  • 13 Kou J P, Tian Y Q, Tang Y K, Yan J, Yu B Y. Antithrombotic activities of aqueous extract from Radix Ophiopogon japonicus and its two constituents.  Biol Pharm Bull. 2006;  29 1267-70

Prof. Guang-ji Wang

Key Lab of Drug Metabolism and Pharmacokinetics

China Pharmaceutical University

Tongjiaxiang street 24

Nanjing 210009

People’s Republic of China

Phone: 86-25-8327-1128

Fax: +86-25-8330-2827

Email: guangjiwang@hotmail.com