Chiral molecules are challenging for the pharmaceutical
industry
because although physical properties of the enantiomers are the same
in achiral systems, they exhibit different effects in chiral systems,
such as the human body. The separation of enantiomers is desired but
complex, as enantiomers crystallize most often as racemic compounds.
A technique to enable the chiral separation of racemic compounds is
to create an asymmetry in the thermodynamic system by generating chiral
cocrystal(s) using a chiral coformer and using the solubility differences
to enable separation through crystallization from solution. However,
such quaternary systems are complex and require analytical methods
to quantify different chiral molecules in solution. Here, we develop
a new chiral quantification method using ultraviolet-circular dichroism
spectroscopy and multivariate partial least squares calibration models,
to build multicomponent chiral phase diagrams. Working on the quaternary
system of (R)- and (S)-2-(2-oxopyrrolidin-1-yl)butanamide
enantiomers with (S)-mandelic acid in acetonitrile,
we measure accurately the full quaternary phase diagram for the first
time. By understanding the phase stabilities of the racemic compound
and the enantiospecific cocrystal, the chiral resolution of levetiracetam
could be designed due to a large asymmetry in overall solubility between
both sides of the racemic composition. This new method offers improvements
for chiral molecule quantification in complex multicomponent chiral
systems and can be applied to other chiral spectroscopy techniques.