In the present work, a new sensitive and selective high-performance liquid chromatography-fluorimetric detection (HPLC-FLD) method was developed and validated to quantify febuxostat (FBX) and montelukast (MON) in human plasma. The developed procedure was successfully applied to a study aimed at evaluating the pharmacokinetic profiles of febuxostat and montelukast in human plasma. A sol-gel poly (caprolactone)-block- poly(dimethylsiloxane)-block-poly(caprolactone) (sol-gel PCAP-PDMS-PCAP) extraction sorbent coated fabric phase sorptive extraction membrane was used in the extraction process. The entire chromatographic analysis was performed with isocratic elution of the composition of the mobile phase (acetonitrile:water, 60:40, v:v, 0.032% glacial acetic acid) on the C18 column. The flow rate is varied during the analysis, particularly from 0.5 mL min(-1) at the start and linearly increased to 1.5 mL min(-1) in 7 min. The detection and quantification of the analytes was carried out by means of a fluorimetric detector at 320 nm and 350 nm as absorption wavelengths and at 380 and 400 nm as emission wavelengths for FBX and MON, respectively. The calibration curves demonstrated linearity in the range 0.3-10 ng mL(-1) and 5-100 ng mL(-1) for FBX and MON, respectively, while the LOD and LOQ values were 0.1 and 0.3 ng mL(-1) for FBX and 1.5 and 5 ng mL(-1) for MON. Intraday and interday RSD% values were found lower than 5.79%. As reported, the method was applied to real plasma samples obtained from a volunteer who was co-administered both the drugs. Pharmacokinetic data reveal that the concentration of both the drugs reaches the plateau approximately at the same time, but exhibits an elimination phase at different rates. This study demonstrated the usefulness of the new method and its applicability in therapeutic drug monitoring (TDM).