1. A positive-negative switching LC-MS/MS method for quantification of fenoldopam and its phase II metabolites: Applications to a pharmacokinetic study in rats.
- Author
-
Du T, Sun R, Siddiqui N, Moatamed L, Zhang Y, Liang D, Hu M, and Gao S
- Subjects
- Animals, Female, Glucuronides blood, Glucuronides metabolism, Glucuronides pharmacokinetics, Limit of Detection, Linear Models, Male, Mice, Inbred C57BL, Rats, Rats, Inbred F344, Rats, Sprague-Dawley, Reproducibility of Results, Sulfates blood, Sulfates metabolism, Sulfates pharmacokinetics, Mice, Chromatography, Liquid methods, Fenoldopam blood, Fenoldopam metabolism, Fenoldopam pharmacokinetics, Tandem Mass Spectrometry methods
- Abstract
Fenoldopam is an approved drug used to treat hypotension. The purpose of this study is to develop and validate an LC-MS method to quantify fenoldopam and its major metabolites fenoldopam-glucuronide and fenoldopam-sulfate in plasma and apply the method to a pharmacokinetic study in rats. A Waters C
18 column was used with 0.1% formic acid in acetonitrile and 0.1% formic acid in water as the mobile phases to elute the analytes. A positive-negative switching method was performed in a triple quadrupole mass spectrometer using Multiple Reaction Monitoring (MRM) mode. A one-step protein precipitation using methanol and ethyl acetate was successfully applied for plasma sample preparation. The method was validated following the FDA guidance. The results show that the LLOQ of fenoldopam, fenoldopam-glucuronide and fenoldopam-sulfate is 0.98, 9.75 and 0.98 nM, respectively. The intraday and interday variance is less than 8.4% and the accuracy is between 82.5 and 116.0 %. The extraction recovery for these three analytes ranged from 81.3 ± 4.1% to 113.9 ± 13.2%. There was no significant matrix effect and no significant degradation under the experimental conditions. PK studies showed that fenoldopam was rapidly eliminated (t1/2 = 0.63 ± 0.24 h) from the plasma and glucuronide is the major metabolite. This method was suitably selective and sensitive for pharmacokinetic and phase II metabolism studies., (Copyright © 2021 Elsevier B.V. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF