Determination of cantharidic acid in rat blood by microdialysis combined with UHPLC-MS/MS

Cantharidic acid (CA) is a typical analogue of cantharidin that has various antitumour activities and low toxicity. Since little is known about the pharmacokinetics of CA, we developed and validated a simple and rapid ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method to determine the concentration of CA present in rat blood microdialysate, and we evaluated its pharmacokinetic parameters. To the best of our knowledge, the present work is the first reported study of CA pharmacokinetics by microdialysis coupled with UHPLC-MS/MS. The microdialysates of CA were separated on a Waters BEH C18 column (2.1 x 50 mm, 1.7 mu m) by using methanol and water at a flow rate of 0.2 mL/min. The quantitative ion transitions under ESI positive ionization mode were m/z 197.1 > 107.0 for CA and m/z 169.1 > 95.0 for norcantharidic acid (internal standard). The calibration range is sufficient for the quantitation of microdialysates samples within the range of 2-200 ng/mL. The intra-day and inter-day bias ranged from -17.0% to 2.3%, and imprecision was less than 16.1%. Six rats received 0.05 mg/kg CA administered intravenously. As calculated by the non-compartment model, the elimination half-life (t(1/2)) and the area under the concentration curve were 1.2 h and 158 h.ng/mL, respectively. (C) 2019 Elsevier B.V. All rights reserved.