Simultaneous Quantification of Filgotinib and Its Active Metabolite in Human Plasma Using Liquid Chromatography–Tandem Mass Spectrometry: Validation and Clinical Application

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Abstract
Filgotinib (FLG) is a Janus kinase 1 inhibitor and is metabolized to an active metabolite, GS‐829845. There is no report on the method for simultaneous quantification of FLG and GS‐829845 in clinical samples. We developed a liquid chromatography–tandem mass spectrometry method for simultaneous determination of FLG and GS‐829845 in patient plasma. FLG and GS‐829845 were extracted from an aliquot of 50 μL of human plasma by simple deproteinization using methanol. Chromatographic separation was performed using a Shim‐pack Scepter C18‐120 column with a combined mobile phase of water and methanol containing 0.1% formic acid and gradient elution at a flow rate of 0.2 mL/min. Detection was performed by positive electrospray ionization using a QTRAP 4500 mass spectrometer. The method was validated in the concentration range of 2.5–50 ng/mL for FLG and 250–5000 ng/mL for GS‐829845. Intra‐ and inter‐day assay accuracy and precision were within 11.4% and 13.9%, respectively. Recoveries and matrix effects were consistent and reproducible. This developed and fully validated method is simple, rapid, and cost‐effective and was used successfully for therapeutic drug monitoring in a patient with rheumatoid arthritis.

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