Pharmacokinetics and bioavailability of gelsenicine in mice by UPLC-MS/MS.

Gelsenicine was one of indole alkaloids isolated Gelsemium elegans Benth. In recent years, the role of Gelsemium elegans Benth preparations in anti-tumor, analgesic, dilatation and dermatological treatment has attracted attention, and it has been applied clinically, but it is easy to cause poisoning. An UPLC-MS/MS method was established to determine the gelsenicine in the mouse blood, and the pharmacokinetics of gelsenicine after intravenous (0.1 mg/kg) and intragastric (0.5, 1 mg/kg) administration was studied. Deltalin was used as internal standard; a UPLC BEH C18 column was used for chromatographic separation. The mobile phase consisted of acetonitrile and 10 mmol/L ammonium acetate (0.1% formic acid) with a gradient elution flow rate of 0.4 mL/min. Multiple reaction monitoring (MRM) mode is used for quantitative analysis of gelsenicine in electrospray (ESI) positive interface. Proteins from mouse blood were removed by acetonitrile precipitation. A validation of this method was in accordance with the US Food and Drug Administration (FDA) guidelines. In the concentration range of 0.05-100 ng/mL, the gelsenicine in the mouse blood was linear (r>0.995), and the lower limit of quantification was 0.05 ng/mL. In the mouse blood, the intra-day precision RSD was less than 12%, the inter-day precision RSD was less than 15%, the accuracy ranged from 89.8% to 112.3%, the average recovery was higher than 76.8%, and the matrix effect was between 103.7% and 108.4%, it meet the pharmacokinetic research requirements of gelsenicine. The UPLC-MS/MS method is sensitive, rapid and selective, and has been successfully applied to the pharmacokinetic study of gelsenicine in mice. The absolute bioavailability of gelsenicine is 1.13%.