Abstract
Bepotastine besilate (here after referred to as BTST), chemically known as ({d(S)4[4[(4chlorophenyl)
(2pyridyl) methoxy] piperidino} butyric acid monobenzene sulphonate), is a second-generation
antihistamine drug. To the best of our knowledge, no studies concerning the isolation
or identification of process-related impurities have been reported so far. The current
study reports the development and validation of a stability-indicating RP-HPLC method
for the separation and identification of 5 potential impurities in bepotastine besilate.
In this experiment, the structures of 3 process-related impurities were found to be
new compounds. They were characterized and confirmed by NMR and MS spectroscopy analyses.
These 3 new compounds were proposed to be (S)-4-[(phenyl)-2-pyridinylmethoxy]-1-piperidinebutanoic
acid,(Imp-A); 4-[(S)-(4-chlorophenyl)-2-pyridinylmethoxy]-1- piperidinebutyric acid,
N-oxide (Imp-B) and (S)-4-[(4- chlorophenyl)-2-pyridinylmethoxy]-1-piperidylethane
(Imp-C). In addition, an efficient optimized chromatographic method was performed
on a Shimadzu Inertsil C8–3 column (150 mm×4.6 mm, 3 μm) to separate and quantify
these 5 impurities. It was using 15 mmol ammonium formate buffer in water (pH adjusted
to 3.8 with formic acid) and acetonitrile as the mobile phase in gradient mode. The
method was developed to separate and quantify these 5 impurities obtained in the range
of 0.05–0.75 μg/mL. It was validated and proven to be selective, accurate and precise
and suitable. It is the first publication of identification and characterization data
of the 3 new compounds. It is also the first effective HPLC method for separation
and quantification of all of process-related impurities in bepotastine besilate.
Key words
drug research - chemistry - anti-inflammatory drugs
