Simple and sensitive Ultra Performance Liquid Chromatography (UPLC) methods were developed, optimized and validated for the determination of 4-Nitro phthalimide, 5-Bromo phthalide and 5-Amino phthalide, 4-Amino phthalimide contents in Citalopram hydrobromide drug substance. All these impurities have been originated from 5-cyanophthalide, a key raw material which is used in the synthetic process of Citalopram. The chromatographic separations were achieved on Acquity UPLC HSS C18 SB, 1.8μm (100 mm x 2.1mm) column maintained at temperature 40°C for the quantification of 4-Nitro phthalimide and 5-Bromo phthalide with a simple mobile phase consisted of 0.01M phosphate buffer at a pH 5.5 and acetonitrile in gradient mode at a flow rate of 0.10 ml/min and monitored at 245nm. Quantification of 5-Amino phthalide and 4-Amino phthalimide were achieved on the same column maintained at temperature 30°C and with same buffer at pH 3.0 and acetonitrile as mobile phase in gradient mode at a flow rate of 0.15 ml/min. These impurities were monitored at 205nm. The analytic methods have been demonstrated through validation experiments. The achieved limit of detection (LOD) values were 1.0, 1.6 ,1.8 and 1.2 ppm, limit of quantification (LOQ) values were 3.0, 5.0, 5.5 and 3.6 ppm and the average accuracy values were 97.9, 102.8, 102.8 & 103.7% for 4-Nitro phthalimide, 5-Bromo phthalide, 5-Amino phthalide and 4-Amino phthalimide respectively.
