Simple, sensitive and selective methods are developed for the spectrophotometric determination of drugs, viz., Cetirizine hydrochloride, Duloxetine hydrochloride, Esmolol hydrochloride, Gemifloxacin, Moxifloxacin and Phenylephrine Hydrochloride based on their reactivity towards Chloramine-T (ChL-T). The method is based on the oxidation of drugs by ChL-T (Excess amount) in presence of acidic medium and estimating the amount of un-reacted ChL-T by Safranin-O (SO) dye at λmax 524 nm. The amount of ChL-T reacted is equal to the drug concentration in this method. The concentration of ChL-T is 10 µgmL-1 and Safranin-O Dye is 10 µgmL-1. The calibration curves obeyed Beer's law over the concentration range of 2.5-17.5 µgmL-1 (CET), 5-35 µgmL-1 (DUL), 12-84 µgmL-1 (ESM), 10-70 µgmL-1 (GEM) & 2.5-17.5 µgmL-1 (MOX). This method has been applied for the determination of drugs in their pure form as well as in tablet formulations. The method has been validated in terms of guidelines of International Conference on Harmonization. INTRODUCTION: Cetirizine dihydrochloride chemically is [2-[4-[(4-chlorophenyl) phenyl methyl]-1 piperazinyl] ethoxy] acetic acid di HCl. Cetirizine di HCl is belonged to the group of the second-generation h1 antagonist, inhibits allergic reaction mediated by histamine.