title: Determination of epacadostat, a novel IDO1 inhibitor in mouse plasma by LC-MS/MS and its application to a pharmacokinetic study in mice.
abstract: A sensitive, specific and rapid LC-ESI-MS/MS method has been developed and validated for the quantification of epacadostat in mouse plasma using tolbutamide as an internal standard (IS) as per regulatory guidelines. Sample preparation was accomplished through a protein precipitation. Chromatographic separation was performed on an Atlantis dC18column using a binary gradient using mobile phase A (acetonitrile) and B (0.2% formic acid in water) at a flow rate of 0.90 mL/min. Elution of epacadostat and IS occurred at ~2.41 and 2.51 min, respectively. The total chromatographic run time was 3.2 min. A linear response function was established in the concentration range of 1.07-533 ng/mL. The intra- and inter-day accuracy and precision were in the ranges of 1.81-12.9 and 3.80-11.1%, respectively. This novel method has been applied to a pharmacokinetic study in mice.
authors.affiliation: Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Bangalore, India.
authors.forename: Vinay
authors.initials: V
authors.lastname: Dhiman
authors.affiliation: Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Bangalore, India.
authors.forename: Kalpesh Kumar
authors.initials: KK
authors.lastname: Giri
authors.affiliation: Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Bangalore, India.
authors.forename: Suresh P
authors.initials: SP
authors.lastname: S
authors.affiliation: Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Bangalore, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Zainuddin
authors.affiliation: Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Bangalore, India.
authors.forename: Sriram
authors.initials: S
authors.lastname: Rajagopal
authors.affiliation: Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Bangalore, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Mullangi
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004791:Enzyme Inhibitors / Q000097:blood*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors*; D057230:Limit of Detection; D008297:Male; D008807:Mice, Inbred BALB C; D010091:Oximes / Q000097:blood*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013449:Sulfonamides / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004791:Enzyme Inhibitors; C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D010091:Oximes; D013449:Sulfonamides; C000613752:epacadostat
keywords: LC-MS/MS; epacadostat; method validation; mouse plasma; pharmacokinetics