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

Xai, Chun-hua, Sun, Jian-guo, Hao, Hai-ping, Wang, Guang-ji, Yan, Bei, Gu, Sheng-hua, Zheng, Chao-nan, Shang, Li-li and Roberts, Michael S. (2008) Quantitative Determination of Ophiopogonin D by Liquid Chromatography/Electrospray Ionization Mass Spectrometry and its Pharmacokinetics in Rat. Planta Medica, 74 15: 1832-1836. doi:10.1055/s-0028-1088339


Author Xai, Chun-hua
Sun, Jian-guo
Hao, Hai-ping
Wang, Guang-ji
Yan, Bei
Gu, Sheng-hua
Zheng, Chao-nan
Shang, Li-li
Roberts, Michael S.
Title Quantitative Determination of Ophiopogonin D by Liquid Chromatography/Electrospray Ionization Mass Spectrometry and its Pharmacokinetics in Rat
Journal name Planta Medica   Check publisher's open access policy
ISSN 0032-0943
Publication date 2008-12-01
Year available 2008
Sub-type Article (original research)
DOI 10.1055/s-0028-1088339
Open Access Status Not yet assessed
Volume 74
Issue 15
Start page 1832
End page 1836
Total pages 5
Editor L. Pieters
Place of publication Stuttgart, Germany
Publisher Georg Thieme Verlag Kg
Language eng
Subject C1
970111 Expanding Knowledge in the Medical and Health Sciences
111504 Pharmaceutical Sciences
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 C(18) 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 ail 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 mu g/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.
Formatted 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.
Key words
Keyword ophiopogonin D
Radix Ophiopogonis
Ophiopogon japonicus Ker-Gawl.
Liliaceae
'SHENMAI' injection
LC-ESI-MS
method validation
pharmacokinetics
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 2003AA2Z347A
30630076
2006BA1081304-05
BK2005098
GJJ08071
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Tue, 31 Mar 2009, 01:14:27 EST by Maree Knight on behalf of School of Medicine