Published:Journal of Chromatographic Science,
ISSN 0021-9665Volume
40, Number 3, March 2002, pp. 170-177
HPLC and LC–MS Studies of the Transesterification Reaction
of Methylparaben with Twelve 3- to 6-Carbon Sugar Alcohols and Propylene Glycol
and the Isomerization of the Reaction Products by Acyl Migration
Minhui Ma, Antonio DiLollo, Robert Mercuri, Tony Lee, Mark Bundang,
and Elizabeth Kwong
Pharmaceutical Research & Development, Merck Frosst Canada & Co., 16711
Trans Canada Highway, Kirkland, Quebec, H9H 3L1, Canada
Sugar alcohols and parabens are commonly used ingredients in
oral suspension formulations. However, their possible incompatibility because
of transesterification reaction is a concern during formulation development.
In order to gain more knowledge about the reaction, a high-performance liquid
chromatographic (HPLC) method is developed to separate the transesterification
reaction products of methylparaben preservative with twelve 3- to 6-carbon sugar
alcohols and propylene glycol. It is found that the number of peaks separated
or partially separated correlate well with the number of distinct hydroxyl groups
present in the sugar alcohol molecules. This means that all the hydroxyl groups
in a sugar alcohol molecule can react with methylparaben to form transesterification
reaction products. These products are positional isomers that have identical
UV spectra with a maximum at 255 nm and the same m/z ratio for molecular ions
by liquid chromatography–mass spectrometry. When isolated individually,
they can isomerize (interconvert) under suitable conditions to form other positional
isomers by intramolecular acyl migration. The acyl migration pathway for each
of the isolated positional isomers from the transesterification reaction of
methylparaben with sorbitol, ribitol, and xylitol is followed by HPLC. Based
on the information, a tentative assignment of the six isomer peaks generated
from the transesterification reaction between methylparaben and sorbitol is
proposed.
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