Abstract

Background: Levocetirizine is chemically know as (R)-(-)-2-[4-(4-chlorobenzhydryl)-1- piperazinyl]-ethoxy acetic acid dihydrochloride. Many publications have reported the synthetic routes of levocetirizine. Several related substances have been detected in levocetirizine hydrochloride drug substances. In our study, a pharmaceutical impurity, at the level of >0.1% w/w, was isolated, purified and identified. It is not included in the European Pharmacopoeia (EP).

Objective: Identification, isolation and characterization of a new pharmaceutical impurity in levocetirizine hydrochloride.

Methods: The impurity was enriched by normal phase silica gel, and was further purified by semipreparative HPLC. It was separated from the crystallization mother liquor of levocetirizine hydrochloride for the first time. Mass spectrometry and nuclear magnetic resonance spectroscopy are the ultimate tools in structure elucidation.

Results: The structure was identified as levocetirizine quaternary ammonium. The formation mechanisms of the impurity are also presented. The method was applied to the determination of the impurity in levocetirizine hydrochloride in real samples.

Conclusion: The method was applied to the determination the impurity of levocetirizine hydrochloride in real samples.

Keywords: Levocetirizine hydrochloride, API, impurity, isolation, semipreparation, structural identification.