A rapid, sensitive, and selective liquid chromatography-mass spectrometry method for simultaneous quantification of astragaloside IV and cycloastragenol in mouse plasma and its application to a pharmacokinetic study

摘要

Astragaloside IV is the primary active ingredient of Astragalus membranaceus (Fisch.) Bunge with multiple pharmacological effects and a promising therapeutic agent for a number of diseases such as diabetic nephropathy and heart disease. To study the pharmacokinetics of astragaloside IV in mice, a rapid, sensitive, and selective liquid chromatography-mass spectrometry method was developed for the simultaneous quantification of astragaloside IV and its main bioactive metabolite, cycloastragenol. Samples were prepared using only 20 mu L of mouse plasma and digoxin as an internal standard. After protein precipitation, the supernatant was treated using a phospholipid removal plate to remove ion-suppressive phospholipids. The analytes and internal standard in the filtered solutions were separated on a C-18 column and detected under positive ion and selected ion monitoring mode within just 3 min. The assay exhibited good linearity in the concentration range 1-200 ng/mL. The intra- and interday precisions expressed as relative standard deviations were all below 8.6%, and the accuracy expressed as a relative error was = 8.8%. The method was successfully applied to a pharmacokinetic study of healthy mice upon administration of 30 mg/kg/d astragaloside IV. (C) 2018 Elsevier B.V. All rights reserved.