A novel UHPLC-MS/MS method for trace level identification and quantification of genotoxic impurity 2-(2-chloroethoxy) ethanol in quetiapine fumarate

AbstractA selective and sensitive new reversed-phase method was developed and validated by using Waters Acquity UHPLC system coupled with Waters Micromass Quattro PremierXE (MS/MS) to identify and quantify the genotoxic impurity 2-(2-chloroethoxy) ethanol at trace level (∼2.0 ppm) in quetiapine fumarate. The method used positive ion electrospray ionization with a multiple reaction monitoring detection mode using ACE3 C18(100 mm × 4.6 mm × 3.0 µm) column. For analysis, an isocratic program was developed using 0.01 M ammonium acetate in Milli-Q water (mobile phase A) and methanol (mobile phase B) in 20:80v/v ratio. Elution of 2-(2-chloroethoxy) ethanol was monitored using triple quadrupole mass spectrometer with an injection volume of 10 μl, a column oven temperature of 40 °C, an auto-sampler temperature of 15 °C, and flow rate of 0.5 mL/min. The retention time of 2-(2-chloroethoxy) ethanol was observed at 2.38 min. The LOQ and LOD were determined at concentrations of 0.235 ppm and 0.070 ppm respectively. The correlation coefficient R2 was 0.9983 and the percent recoveries of method range from 98.1% to 114.0%. The method was successfully validated according to International Council for Harmonization requirements (ICH Q2(R1) and ICH M7(R1)) for genotoxic impurities. The method was sensitive, selective, accurate and precise and therefore can be used for identification and quantification of genotoxic impurity 2-(2-chloroethoxy) ethanol in quetiapine fumarate.Keywords: 2-(2-chloroethoxy) ethanolgenotoxic impurityquetiapineUHPLC-MS/MSMultiple reaction monitoring (MRM) Disclosure statementNo potential conflict of interest was reported by the author(s).AcknowledgementsThe authors thank the management of Kshetra Analytics Ltd (Hyderabad, TS, India) and Jawaharlal Nehru Technological University, Anantapur (AP, India) for their support and encouragement to conduct this research.The author’s own views were expressed in this paper. The authors Shaik Mahammad Ali and Manchuri Krishna Moorthy are currently working for Novartis Health Care Pvt Ltd, Hyderabad, India.