Determination of Poricoic Acid A in Rat Plasma after Oral and Intravenous Administration by LC-MS-MS and Its Application to a Pharmacokinetic Study
2010
Yin, Lian-Hong | Xu, Li-Na | Han, Xu | Xu, You-Wei | Qi, Yan | Peng, Jin-Yong
A sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed and validated for the quantification of poricoic acid A (PAA) in rat plasma. The plasma samples were precipitated by protein precipitation with methanol. Glycyrrhetic acid was used as the IS. Chromatography was performed on a Dionex C₁₈ 120 Å (4.6 × 250 mm, 5 μm) column with the mobile phase composed of acetonitrile-water (90:10, v/v) at a flow rate of 0.8 mL min⁻¹. A tandem mass spectrometer equipped with an ESI source was used as the detector and was operated in the negative ion mode. Quantification was performed using multiple reaction monitoring (MRM) of the transitions m/z 497.4 → 423.3 and m/z 469.2 → 425.1 for PAA and IS, respectively. The calibration curves were linear over the range of 5-5,000 ng mL⁻¹ (r ² = 0.9966) and the lower limit of quantification (LLOQ) was 5 ng mL⁻¹. In this range, RSDs were <10% for intra-assay and inter-assay precisions. The accuracy expressed by deviation (DEV) was <6%, and the extraction recoveries of QC samples were >78%. The validated method was successfully used to study the pharmacokinetics of PAA in rats after intravenous administration at a dose of 1.0, 2.5 and 5.0 mg kg⁻¹ and oral administration at a dose of 25, 50 and 100 mg kg⁻¹, respectively. The relative bioavailability of PAA in rats following oral administration was achieved.
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