Indirect Determination of Process Impurity Cetrimonium Bromide in Neisseria meningitidis A/C/Y/W-135-DT Conjugate Vaccine by HPAEC-PAD Method

Abstract

A validated High Performance Anion Exchange- Pulsed Amperometric Detection (HPAEC-PAD) indirect method is described to determine traces of process impurity cetrimonium bromide (CTAB) in Neisseria meningitidis A/C/Y/W-135-DT conjugate vaccine. Method reported here, measures the bromide ion present in CTAB. As part of impurity profiling, samples of crude and purified meningococcal four serogroup (A, C, W-135 and Y) polysaccharides and final vialed conjugate vaccine were analyzed for CTAB content. Vaccine grade pure polysaccharides, the control and the final vaccines both formulated in phosphate buffered saline (PBS) showed sub ppm levels of CTAB impurity. PBS used in this work showed detectable bromide levels presumably due to contamination originated from saline. The proposed method is very sensitive (LOD=0.04 ppm, LOQ =0.11 ppm), accurate, reproducible and compatible with polysaccharide and PBS environments.