Recently I had the privilege of giving a lecture at the
annual Eastern Analytical Symposium in Plainsboro Township, NJ. This year, the
symposium was held in an elegant new venue, the Crowne Plaza
Princeton-Conference Center. I have been attending EAS since 2011 and I think
this has been my favorite one so far.
My
presentation was at 11:00am on Wednesday the 15th. The subject of my
lecture was about a method my colleagues and I had been working on for
chromatographic assay and organic impurities detection of chlorpheniramine
maleate formulations. The current USP method calls for a time-consuming
multistep liquid–liquid extraction procedure for the assay, and no method is
provided for impurities analysis. Consequently, there was a lot of room for
improvement in bringing these methods up-to-date.
As a basic compound,
chlorpheniramine may be prone to prone to chromatographic tailing via undesirable
electrostatic interaction with residual silanols present on the surface of some
traditional silica-based stationary phases. Hence, the moderately hydrophobic
Si–H-based surface of Cogent™ columns was postulated to be advantageous in
terms of minimizing tailing contributions from this phenomenon.
We
encountered a few obstacles in method development. The first involved peak
splitting for the first two peaks. I had previously selected a diluent with 50%
acetonitrile in an effort to ensure solubility of the more hydrophobic
analytes, but this choice had the undesired effect of peak splitting. Reducing
the organic content in the diluent to 10% resolved this issue. Another
encountered problem dealt with trying to use a high enough extract
concentration such that we could detect impurity peaks at the 0.1% level while
being careful not to overload the column so much that we lost resolution of the
critical peak pair. In this case, adjusting the gradient and using a lower
mobile phase concentration of trifluoracetic acid (0.05% instead of 0.1%)
helped to improve selectivity enough that resolution was sufficient at the
higher extract concentration.
Despite
these setbacks, we produced a nice method for subsequent validation studies and
I think the audience was quite pleased with the end result. This was my second
year as a speaker at EAS and look forward to the opportunity to possibly
present again at future meetings! Hope to see you there in 2018!
