2 research outputs found
Online Inductive Electrospray Ionization Mass Spectrometry as a Process Analytical Technology Tool To Monitor the Synthetic Route to Anagliptin
Inductive
electrospray ionization (iESI) is an ambient ionization
method that is particularly well-suited to online reaction monitoring.
It allows the potential of electrospray mass spectrometry (MS) to
be realized as a routine process analytical technology (PAT) tool
to monitor practical synthetic reactions in real time. In this study,
a synthetic route to Anagliptin (target API) was successfully monitored
using online iESI-MS. Starting materials not seen by traditional reaction
monitoring tools (HPLC-UV/Vis and GC-FID) were observed, as well as
water-sensitive reagents and intermediates which cannot easily be
followed by other methods. Online tandem mass spectrometry (MS/MS)
was used to characterize chemical species in the reaction mixture.
Impurities and byproducts were identified, and information on the
progress of byproduct formation enabled implementation of strategies
to eliminate these byproducts in the course of the reaction. This
work demonstrates how iESI-MS can be employed to obtain comprehensive
information and solutions to some practical problems that occur in
small-molecule synthetic reaction monitoring
Simultaneous Online Monitoring of Multiple Reactions Using a Miniature Mass Spectrometer
Advances in chemical
sampling using miniature mass spectrometer
technology are used to monitor slow reactions at a frequency of ca.
180 h<sup>–1</sup> (on the Mini 12) with no sample carryover
and with inline derivatization in the case of poorly ionizing compounds.
Moreover, we demonstrate high reproducibility with a relative error
of less than 10% for major components. Monitoring is enabled using
a continuous-flow nanoelectrospray (CF-nESI) probe contained in a
custom-built 3D-printed rotary holder. The holder position is automatically
set using a stepper motor controlled by a microcontroller. Reaction
progress of up to six reactions, including hydrazone formation and
Katritzky transamination, can be monitored simultaneously without
carryover for several hours