Development of an LC–MS/MS method for the quantitation of deoxyglycychloxazol in rat plasma and its application in pharmacokinetic study

摘要

Deoxyglycychloxazol(TY501) is a glycyrrhetinic acid derivative which exhibits high anti-inflammatory activity and reduced pseudoaldosteronism compared to glycyrrhetinic acid.In this study,a sensitive and rapid liquid chromatography–tandem mass spectrometry(LC–MS/MS) method was established for the quantitation of TY501 in rat plasma.Plasma samples were treated by precipitating protein with methanol and supernatants were separated by a Symmetry C_8 column with the mobile phase consisting of methanol and 10 m M ammonium formate(containing 0.1% of formic acid)(90:10,v/v).The selected reaction monitoring(SRM) transitions were performed at m/z 647.4-191.2 for TY501 and m/z 473.3-143.3 for astragaloside aglycone(IS) in the positive ion mode with atmospheric pressure chemical ionization(APCI) source.Calibration curve was linear over the concentration range of 5–5000 ng/m L.The lower limit of quantification was 5 ng/m L.The mean recovery was over 88%.The intra- and inter-day precisions were lower than 6.0% and 12.8%,respectively,and the accuracy was within 7 1.3%.TY501 was stable under usual storage conditions and handling procedure.The validated method has been successfully applied to a pharmacokinetic study after oral administration of TY501 to rats at a dosage of 10 mg/kg.