Two novel, fast, and simple spectrophotometric and HPLC procedures were developed for the determination of telmisartan and estradiol valerate by magnetic solid-phase extraction (SPE) using magnetic Fe3O4 nanoparticles (MNPs) modified by cetyltrimethylammonium bromide (CTAB) as an extractor and methanol was used as desorption. Effects of different parameters influencing the extraction efficiency of drugs were investigated and optimized. Spectrophotometric method was monitored at λmax 230 and 209 nm with detection limit 0.016 and 0.087 μg mL-1 for telmisartan and estradiol valerate, respectively. HPLC method was developed with detection limits 1.63 and 7.02 ng mL-1 for telmisartan and estradiol valerate, respectively. Finally, the proposed method has been effectively employed in extraction and determination of the drugs in pure form, in pharmaceutical formulations. Telmisartan can be extracted and determined in mixture with hydrochlorothiazide, and also estradiol valerate can be analyzed in mixture with norgestrel by the two cited methods.