Herein, fabric phase sorptive extraction – a member of sorbent-based microextraction family – is utilized for the rapid isolation of selected antiviral drugs namely amantadine, memantine and rimantadine from human urine prior to their analysis with UHPLC-MS/MS. Fabric phase sorptive extraction membrane coated with sol–gel sorbent coated poly(propylene glycol)-poly(ethylene glycol)-poly(propylene glycol) sorbent was identified as the optimum extraction membrane for the target analytes. Due to the engineered affinity of the fabric phase sorptive extraction towards the analytes, the extraction proceeds in relatively short time (20 min) while its high permeability permits the extraction of biological samples without any other pretreatment. Following selection of the appropriate membrane, significant parameters including extraction time, sample volume, membrane size, elution solvent, etc were optimized. The drugs were analyzed under positive electrospray ionization using multi-reaction monitoring mode. The method was linear in the range of 5 – 100 ng mL−1 by constructing weighted matrix-matched calibration curves. The intra-day and inter-day accuracy were ranged between – 18.7 to + 18.1% and – 18.3 to + 16.1%, respectively. The precision of the method (intra-day, inter-day) were less than 18.5 % in all cases. The method limits of detection were in the range of 0.2 – 0.8 ng mL−1 while the lower limit of quantitation was set at 5 ng mL−1 for all analytes. The developed analytical scheme was efficiently applied to the analysis of the target drugs in human urine and could be adopted as a rapid and robust green analytical tool for clinical applications.