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.
ophiopogonin D - Radix Ophiopogonis -
Ophiopogon japonicus Ker-Gawl. - Liliaceae - ’SHENMAI’ injection - LC-ESI-MS - method validation - pharmacokinetics
