Development and Validation of the Head Space Gas Chromatography Method for the Simultaneous determination and Quantification of Organic Volatile Impurities in Citalopram Hydro Bromide API and its Pharmaceutical Dosage Forms

This article describes a simple and rapid gas chromatographic method for identification and quantification of organic volatile impurities present in Citalopram hydro bromide and its pharmaceutical dosage forms. The organic solvents such as Iso-propyl alcohol (IPA), tetra hydro furan (THF), benzene, toluene and dimethyl formamide (DMF) are frequently used in manufacturing of Citalopram hydro bromide. Even after such manufacturing process, some solvents still remain in small quantities. Method for the quantification of residual solvents present in Citalopram hydro bromide was done by head space gas chromatography with flame ionization detector and utilizes the Shimadzu GC- 2010 with FID (ZB-624, 30 m × 0.53 mm, 3 μ) capillary column, nitrogen as carrier gas with a flow rate of 3.0 mL/min. The critical experimental parameters such as oven temperature, zero air, make up flow, injection temperature; split ratio, head space conditions and the selection of diluent were studied and optimized. The retention time of various residual solvents taken individually and in spiked standard solutions were determined. The retention times are5.86min for IPA,8.51min for THF,9.22 min for benzene,11.26 for toluene and 12.41 min for DMF respectively. The proposed method was statistically validated as per standard ICH guidelines. The % RSD for six injections should be NMT 10%. The percentage recovery ranges from 85-115%. The correlation coefficient (R²) is NLT 0.99. The LOD and LOQ was found to be specific. Precision, method precision and intermediate precision was found to be within the acceptance limit.From the obtained validation results the proposed method has been successfully applied for the quantification of organic volatile impurities present in citalopram hydro bromide API and its pharmaceutical dosage forms