DETERMINATION OF PROCESS RELATED GENOTOXIC IMPURITIES OF SALBUTAMOL SULPHATE BY LC METHOD

Abstract

The main aim of this research work is to develop a suitable LC method for the quantitative determination of genotoxic impurities contains in Salbutamol Sulphate which is coming from the chemicals used during the manufacturing process. In manufacturing process many unwanted chemical materials are being used and out that many are following under Genotoxic category. After screening and doing the assessment on the genotoxic predication in salbutamol sulphate. The possible genotoxic impurities identified and likely to present in salbutamol Sulphate as Salicylic acid,[1][2][3] Acetyl methyl Salicylate (AMS),[4][5][6] Benzyl methyl salicylate (BMS),[7] Bromo-compound[8] and Dibromo-compound[8]. The main challenge is to separate all impurities from each other to get better resolution and response. As genotoxic[19][24] impurities estimation limit in final molecule is very minute and low it is not easy to quantify at ppm level present in Salbutamol sulphate in Active Pharmaceutical Ingredients. Hence the LC method was developed on Waters HPLC system (Water’s Ltd, USA) with 2995 UV detector at 273 nm as wavelength and 1.0 ml/min flow rate by using Spherical end-capped octylsilyl silica gel for chromatography (l = 0.15 m, Ø = 4.6 mm, 3µm) long with gradient system. The chromatographic and integrated data were recorded using Empower -3 data acquisition software. The limit of detection and the limit of quantitation for the impurity were established. Validation of the developed LC method was carried out as per ICH requirements and the data shows that the proposed method is specific, linear, accurate, precise and robust. This method has been tested in a number of Salbutamol Sulphate and used successfully for quantification of the reported impurities at ppm level. The developed LC method was found to be suitable to quantify the genotoxic impurities Salicylic acid, Acetyl methyl Salicylate (AMS), Benzyl methyl salicylate (BMS), Bromo-compound and Dibromo-compound at ppm level present Salbutamol Sulphate.