¹Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia DOI : 10.35333/jrp.2020.145 The presence of tartrazine, yellow coloring agent, suspected to interfere with the CPM determination in CPM tablets using direct spectrophotometry or high performance liquid chromatography. Overlap spectra of tartrazine and CPM at an analytical wavelength and peak tailing were the main problem occurs in CPM tablets analysis. The aim of this study was to develop a derivative UV spectrophotometry and a modified HPLC to overcome the problem in CPM tablet analysis. Both validated methods were applied for the determination of CPM content in three registered CPM tablets. As a result, the first derivative spectrophotometry method obtained the δA/δλ of tartrazine in matrix tablet was nearly zero at the wavelength of 232 nm and did not interfere with the δA/δλ of CPM. The selective mobile phase for separation of CPM from tartrazine using HPLC method was a mixture of phosphate buffer pH 4 and methanol (60:40 v/v) with a flow rate of 1 ml/min. The CPM separated from tartrazine and other peaks in sample(s) with Rs of >1.5 The linearity, accuracy, and precision of these two methods fulfilled the reference requirement. No significant difference observed between the CPM content in artificial tablets when analyzed using first-derivative spectrophotometry and HPLC method. The concentration of CPM in one registered tablet that had been assayed using spectrophotometry, HPLC and the standard method was not significantly different. As a conclusion first-derivative spectrophotometry and HPLC method were valid for the determination of CPM in a tablet containing tartrazine. However, the first-derivative spectrophotometry method was more efficient than HPLC. Keywords : Chlorpheniramine maleate; tartrazine; UV-spectrophotometry; HPLC; method validation