An Accurate and Precise Analytical Method for Estimation of Active Sulfur Trioxide and Sulfuric acid in Triethylamine Sulfur Trioxide Complex

Abstract

Triethylamine sulfur trioxide complex (TEA-SO3) is an important sulfating agent used in the synthesis of various drug substances, dyes and other chemicals. Quality of TEA-SO3 is very crucial because it provides the active sulfur trioxide (SO3) in the sulfation reaction. We developed an accurate, precise and robust analytical method for determination of quality of TEA-SO3. The potentiometric titrimetry methods are capable to estimate SO3 as well as degradation product sulfuric acid (H2SO4) present in the TEA-SO3. Estimation of SO3 involves hydrolysis of the complex using H2SO4 under reflux condition and titrating excess H2SO4 against alkali solution. H2SO4 is quantified by direct titration against alkali solution. Both assay and impurity quantification methods were validated as per the ICH guideline. Accuracy of H2SO4 determination was 102.80% with precision of 0.75% and could be detected as low as 0.01%. Method to estimate SO3 was accurate with recovery of 99.92% and precision of 0.25%. The developed methods were employed for quality check of the reagent.