Sensitive quantitation of residual phenylhydrazine in antipyrine by LC-ICP-MS with iodo derivatization.

Phenylhydrazine is a genotoxic impurity commonly used as a raw material in active pharmaceutical ingredients. In this study, a novel method, using inductively coupled plasma-mass spectrometry combined with two-dimensional liquid chromatography (LC-ICP-MS), was employed for the quantitation of residual phenylhydrazine in antipyrine. The compound 2,3,5-triiodobenzoyl chloride, which contains three iodine atoms, was investigated as a derivatization reagent. The DL 0.06 ppm was obtained, and the method was applied to the quantitation of residual phenylhydrazine in antipyrine. No residual phenylhydrazine was detected in five lots of antipyrine obtained from the commercial source.