posted on 2021-07-02, 15:34authored byYusuke Sato, Junliang Liu, Andrew J. Kukor, Jeffrey C. Culhane, John L. Tucker, David J. Kucera, Brian M. Cochran, Jason E. Hein
Solid–liquid slurries are
vital and increasingly prevalent
in the pharmaceutical and chemical industries. Despite the importance
of these heterogeneous systems, process control and optimization are
fundamentally hindered by a lack of compatible real-time analytical
techniques. We present herein an online HPLC monitoring platform enabling
access to real-time compositional information on slurries. We demonstrate
the system by investigating the heterogeneous synthesis reaction of
tetrabenazine. Furthermore, we integrated our online HPLC platform
with the orthogonal monitoring techniques of a pH probe and a microscopic
imaging probe to provide additional mechanistic insight. These combined
insights enable the optimization of tetrabenazine synthesis in terms
of reaction time, byproduct formation, and diastereomeric purity of
the final product.