Category: Formulation and Quality
Purpose: Alkyl sulfonates have been widely concerned as genotoxic impurities (GTIs). Analytical challenge of developing sensitive and robust methodology for the determination of sulfonate esters as well as control challenge in API production are required for the pharmaceutical industry. In the study, a liquid injection GC-MS/MS method with MRM mode was applied to investigate 9 alkyl sulfonates simultaneously.
Methods: Nine alkyl sulfonates were used as target analytes in the study. Column selectivity was performed on Shimadzu GC 2010 with flame ionization detector (FID). Analysis was carried out on a GC-MS-MS system (Agilent 7890B GC system coupled with Agilent 7000D Triple Quadrupole mass spectrometer). The method for quantification of the 9 sulfonate esters using GC-MS/MS with MRM mode was validated.
Results: The method was validated in terms of linearity, sensitivity, injection precision, accuracy and solution stability. The limit of quantitation (LOQ) for the 9 commonly encountered sulfonate esters in drug substances was within 0.10-1.05 ng/mL, which was much lower than the reported LOQs in other methods (2.5-1500 ng/mL). It is indicated that the method gave extremely high sensitivity for all the target analytes. The correlation coefficient (r) values of 9 GTIs were no less than 0.9993 in the range of 2.0-100 ng/mL. All alkyl sulfonates were stable in these three solvents up to 36 hours.
Conclusion: This method has been successfully used for determination of alkyl sulfonates in capecitabine and imatinib methanesulfonate. Meanwhile, the developed method achieved extremely high sensitivity for all the target analytes and can be further applied to other drug substances.