Abstarct: In this study, for the first time a simple, rapid, and highly efficient liquid-phase microextraction method baxsed on the vortex-assisted emulsification solidified floating organic drop, followed by high performance liquid chromatography equipped with UV detection, has been developed for simultaneous preconcentration and determination of Ticlopidine (Tic) and losartan (Los). In this method, a few microliters of 1-dodecanol was delivered to the surface of solution containing trace amounts of Tic and Los. Then this solution was vortexed for a desired time. Then sample solution was cooled by inserting it into an ice bath for a short time. The solidified 1-dodecanol containing analytes was transferred into a suitable vial and immediately melted, it was diluted by 5.0µl of methanol and injected to HPLC. Full factorial design was used as Screening method to select the important variables that effect extraction efficiency. Then Central composite face-centered design (CCF) was used for optimization of selected factors by Full factorial design such as pH and volume of organic solvent. The calibration curves were linear in the range of 0.006-5.5 ppm for Tic and 0.004-4.5 ppm for Los. Under the optimum conditions, the detection limits were 1.7 ppb for Tic and 1.0 ppb for Los. Preconcentration factor were 99.5 for Tic and 153.8 for Los. The relative standard deviation for five replicate measurements of 1.0 and 4.0 ppm of Tic and Los were obtained 1.1 and 0.8 %, 1.8 and 0.5% respectively.