LC-MS METHOD DEVELOPMENT AND VALIDATION FOR THE LOW-LEVEL DETERMINATION OF GENOTOXIC IMPURITY, ETHYL P-TOLUENE SULFONATE IN PERIN-DOPRIL TERT-BUTYLAMINEAbstract
Objective: Ethyl para toluene sulfonate is a genotoxic impurity and the current work’s primary objective is to develop a hyphenated and highly sensitive LC-MS method for the determination (EPTS) in Perindopril tert-butylamine. Method: EPTS was determined by LC-MS method in selective ion monitoring mode (SIM) using Atlantis T3 (150×4.6mm) 3.0 µm column. 0.01M ammonium acetate is utilized as buffer. Gradient elution was employed and the Mobile phase A is composed of mixture of buffer and methanol in 70:30 (v/v) ratio along with Mobile phase B made up of buffer and methanol in 5:95 (v/v) ratio. The gradient program (T/%B) was set as 0/5, 2.50/5, 7.00/50, 12.00/70, 18.00/95, 21.00/95, 24.00/5, 30.0/5. Results: The LOD and LOQ values found for EPTS were 0.018 µg/mL and 0.054 µg/mL. The method has accuracy within 98.1-103.5% for the analyte. Developed method validated as per International Conference on Harmonization guidelines. Conclusion: Developed LC-MS method in SIM mode can be applied as a good quality control tool for quantitation of EPTS impurity at very low levels in Perindopril tert-butylamine.
S. K. Susarla *, S. Duvvuri and B. M. Rao
Gandhi Institute of Technology and Management, Visakhapatnam, Andhra Pradesh, India.
06 December 2019
26 February 2021
18 March 2021
01 April 2021