Abstract
Platycodon grandiflorum has long been used as a traditional oriental medicine for respiratory disorder. Platycodin D (PD) is known as the main component isolated from the root of PG. A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantitation of PD in rat plasma. Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization and multiple reaction monitoring in positive ion mode. The total chromatographic run time was 4.0 min, and the calibration curves of PD were linear over the concentration range of 50–10,000 ng/mL in rat plasma. The coefficient of variation and relative error at five QC levels were 1.0 to 8.8% and 0.7 to 8.7%, respectively. After a single oral administration of 500 mg/kg and a single intravenous administration of 25 mg/kg of 3% PD extract (a PG extract including 3% of PD), platycodin D and platycodin D3 were detected and pharmacokinetic parameters were estimated. The oral bioavailability of platycodin D and platycodin D3 was 0.29% and 1.35% in rats at 500 mg/kg of 3% PD extract of PG, respectively. The present method can be applied to pharmacokinetic analysis of platycodins and platycosides of the PG.
Highlights
Platycodi Radix, the root of platycodon grandiflorum (PG), is used extensively as an anti-inflammatory agent in the treatment of respiratory symptoms such as cough, sore throat, bronchitis, and bronchial asthma [1]
The chemical structures of Platycodin D (PD), Platycodin D3 (PD3), and IS are shown in Figure 1, and those were ionized under our electrospray conditions, and ionized analytes could be sensitively detected by a mass spectrometer in positive ion mode
MRM transitions for PD (m/z 1247.7 to m/z 705.2), PD3 (m/z 1409.9 to m/z 867.5), and IS (m/z 955.4 to m/z 775.4) were determined and various parameters for mass spectrometer were optimized by a direct infusion study of a PD standard solution
Summary
Platycodi Radix, the root of platycodon grandiflorum (PG), is used extensively as an anti-inflammatory agent in the treatment of respiratory symptoms such as cough, sore throat, bronchitis, and bronchial asthma [1] Some saponins such as platycodins (A, D, D2, and D3), polygalacin D2, platyconic acid A, and platycosides (A, B, C, D, E, and F) are separated from Platycodi Radix [2,3,4,5]. Platycodin D has been reported to inhibit COX-2 induction by 12-O-tetradecanoylphorbol-13-acetate (TPA) and to suppress the production of prostaglandin E2 in rat peritoneal macrophages [11, 12] The determination of these bioactive platycosides has been carried out mainly by traditional high performance liquid chromatography (HPLC) using a UV detector [6, 13] or an evaporative light scattering detector (ELSD) [4, 14]. Since saponins including platycosides have very unique properties such as very weak absorbance even at short wavelengths, high polarity, thermal lability, and very low volatility, their analyses based on traditional HPLC techniques are complicated [4]
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