Reliable and Easy-To-Use Liquid Chromatography-Tandem Mass Spectrometry Assay for Quantification of Olorofim (F901318), a Novel Antifungal Drug, in Human Plasma and Serum

Antimicrobial Agents and Chemotherapy
Carsten MüllerMartin H J Wiesen

Abstract

A fast and easy-to-use liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination and quantification of a novel antifungal drug, olorofim (F901318), a member of the novel class of orotomides, in human plasma and serum was developed and validated. Sample preparation was based on protein precipitation with acetonitrile and subsequent centrifugation. An isotope-labeled analogue of F901318 was employed as an internal standard. Chromatographic separation was achieved using a 50-mm by 2.1-mm, 1.9-μm, polar Hypersil Gold C18 column and isocratic mobile phase consisting of 0.1% formic acid-acetonitrile (60%-40%, vol/vol) at a flow rate of 330 μl/min. The analyte was detected using a triple-stage quadrupole mass spectrometer operated in selected reaction monitoring (SRM) mode with positive heated electrospray ionization (HESI+) within a single runtime of 2.00 min. The present LC-MS/MS method was validated according to the international guidelines of the International Conference on Harmonisation (ICH) and the U.S. Food and Drug Administration (FDA). Linearity of F901318 concentration ranges was verified by the Mandel test. The calibration curve was tested linear across the range and fitted using least-squares ...Continue Reading

References

Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Jason D OliverMike Birch
Mar 24, 2017·The Journal of Antimicrobial Chemotherapy·Nathan P WiederholdMichael Birch
Jun 13, 2017·The Journal of Antimicrobial Chemotherapy·J B BuilP E Verweij
Sep 12, 2017·International Journal of Antimicrobial Agents·Nathan P Wiederhold
Sep 19, 2017·Infection and Drug Resistance·Nathan P Wiederhold

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Citations

Feb 27, 2020·Open Forum Infectious Diseases·Adriana M RauseoAndrej Spec

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