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摘要
A rapid, robust and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for bioanalysis of TJ0711, a novel vasodilatory -blocker in dog plasma. This assay is able to chromatographically separate TJ0711 from its isobaric metabolite as well as glucuronide conjugates. Chromatographic separation was achieved on a Welch Ultimate-XB C-18 column (2.1 x 100mm, 3m). The analyte and internal standard (propranolol) were extracted from plasma by liquid-liquid extraction using ethyl acetate. The mass spectrometric detection was carried out in positive ion multiple reaction monitoring mode. Good linearity was obtained over the concentration range of 0.5-500ng/mL (r > 0.99) for TJ0711. Moreover, the method had good accuracy (RE ranging from -2.70 to -0.32%) and precision (RSD < 7.55%). TJ0711 was stable in dog plasma for at least 6h at ambient temperature, for at least 30days at -20 degrees C and after three freeze-thaw cycles. This method was successfully applied to a preclinical pharmacokinetic study and the results demonstrated linear pharmacokinetics of TJ0711 over a dose range from 0.03 to 0.3mg/kg. No significant gender differences were observed in TJ0711 plasma pharmacokinetic parameters.
- 出版日期2018-6
- 单位华中科技大学
