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Determination of residual 4‐nitrobenzaldehyde in chloramphenicol and its pharmaceutical formulation by HPLC with UV/Vis detection after derivatization with 3‐nitrophenylhydrazine

Lan Luo,Congcong Gu,Mingxian Li,Xiangyuan Zheng,Feng Zheng

Published 2018 in Journal of Pharmaceutical and Biomedical Analysis

ABSTRACT

HighlightsA HPLC‐UV derivatization analysis method for 4‐nitrobenzaldehyde is proposed.To control 4‐nitrobenzaldehyde as potential genotoxic impurity by HPLC for the first time.Four nitro‐substituted phenylhydrazines as derivatization reagent are compared.3‐nitrophenylhydrazine shows a significant advantage in maximizing the redshift.Application of the method is performed for chloramphenicol and its formulation. ABSTRACT 4‐Nitrobenzaldehyde is the synthetic raw material and an important photodegradation product of chloramphenicol. With a structural “alert” of human genotoxic potential and reported mutagenicity, this compound should be controlled in drug substances as a potential genotoxic impurity. However, current analysis methods require complex pre‐treatment processes and/or lack sufficient specificity and sensitivity. Nitrophenylhydrazine is a common carbonyl derivatization reagent used to determine the residual aromatic aldehydes in drug samples. In the present study, we report an unexpected advantage of 3‐nitrophenylhydrazine hydrochloride as a derivatization reagent in the derivatization high‐performance liquid chromatography‐ultraviolet detection method to determine 4‐nitrobenzaldehyde in chloramphenicol samples. Compared with other nitro‐substituted phenylhydrazines, 3‐nitrophenylhydrazine hydrochloride can minimize drug matrix and derivatization reagent interferences, since the maximum absorption wavelength of its derivative is significantly red‐shifted to 397 nm. The derivatization conditions have been optimized in terms of reaction efficiency, including reaction temperature, time, and diluting solvent, through a design of experiments. As a result, after reaction with 500 &mgr;g mL−1 of 3‐nitrophenylhydrazine hydrochloride in acetonitrile‐water (70:30, v/v) at 60 °C for 30 min, the developed HPLC method could be used to determine 4‐nitrobenzaldehyde with a limit of detection of 0.009 &mgr;g mL−1. The method was then validated and applied for the determination of residual 4‐nitrobenzaldehyde in chloramphenicol and its eye‐drop samples.

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