A novel flow injection method was developed for the determination of Penicillamine (PA), Ephedrine (EP) and chlorpheniramine (CPA). The method is based on the reaction of each analyte with tris(2,2'-bipyridyl) ruthenium (II) (Ru(bipy)32+) and peroxydisulfate in the presence of light to produce chemiluminescence, PA and EP were determined after derivatization with acetaldehyde and formaldehyde respectively. This derivatization step results in significant enhancement of the chemiluminescence signal, leading to the better sensitivity and lower detection limits. The FI configuration consisted of a multiposition (eight ports) valve and a syringe pump for aspiration of the reagents ( ruthenium complexes and peroxydisulfate) and a peristaltic pump used to propel the sample solution. Experimental factors that influence the derivatization reaction and the CL reaction were systematically optimized. Under the optimum conditions, linear calibration curves between 0.2 - 24 ppm, 0.2 - 20 ppm, 0.1 -14 ppm, for PA, EP and CPA were obtained. The detection limits were 0.1ppm, 0.03 and 0.01 ppm for PA, EP and CPA respectively. For the first time, the oxidation of tris(1,10-phenanthroline) ruthenium(II) by peroxydisulfate in the presence of light was used to determine CPA. The calibration curve was linear between 0.1 - 10 ppm and detection limit of 0.04 ppm for CPA was obtained. When applied to pharmaceutical formulations, the procedures were found to be free from interferences from common excipients except chlorpheniramine in syrup where we apply standard addition. The results obtained for the assay of commercial formulations demonstrated good accuracy and precision.