Pharmacokinetics, tissue distribution and plasma protein binding rate of palmatine following intragastric and intravenous administration in rats using liquid chromatography tandem mass spectrometry

Abstract

Palmatine is a natural isoquinoline alkaloid widely found in traditional Chinese medicines. In this study, a simple, sensitive and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the quantification of palmatine in the plasma and tissue samples in rats. Sample preparation involved a simple protein precipitation extraction technique using acetonitrile as the precipitating solvent. Chromatographic separation was accomplished on an ACQUITY UPLC BEH C18 column with a mobile phase of acetonitrile-5 mM ammonium acetate solution (70:30, v/v) at a flow rate of 0.3 mL/min. Coptisine was selected as the internal standard. The protonated analytes were determined with MRM in the positive ion mode. The assay exhibited a linear dynamic range of 1.0−1000 ng/mL for palmatine in each biological matrix and the low limit of quantification was 1.0 ng/mL. Non-compartmental pharmacokinetic parameters indicated that there is a significant difference in the apparent distribution volume and half-life between intragastric and intravenous administration modes. Palmatine could be detected in different tissues and the content in liver and kidney is relatively high, suggesting that liver and kidney might be the targeting organs of palmatine. The plasma protein binding rate test showed that the percent binding of palmatine is medium, and was found to be higher in human than in rats.