In this work, we investigated the "in vitro" interactions of prazosin with frequently prescribed and co-administered drugs in simulated human body environments and thus to infer about the combination therapy. The interacting drugs selected for interaction with prazosin are ACE-inhibitors (captopril, enalapril and lisinopril), calcium channel blockers (amlodipine, diltiazem and verapamil), H2 receptor antagonists (cimetidine, famotidine and ranitidine), NSAID's (diclofenac sodium, flurbiprofen, mefenamic acid, meloxicam and naproxen), statins (atorvastatin, rosuvastatin and simvastatin) and hydrated salts of essential and trace elements (magnesium, calcium, chromium, manganese, ferric, cobalt, nickel, copper, zinc and cadmium). These interactions were conducted in simulated gastric juice (pH 1), simulating full stomach (pH 4), simulating blood pH (pH 7.4) and simulating intestinal pH (pH 9) using UV/visible spectrophotometric and reversed phase high performance liquid chromatography (RP-HPLC).Prior to start the drug interaction studies, assay methods for the simultaneous quantitation of prazosin and interacting drugs were developed using UV/UV/visible spectrophotometer and RP-HPLC.