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Small footprint liquid chromatography-mass spectrometry for pharmaceutical reaction monitoring and automated process analysis

journal contribution
posted on 2023-05-21, 10:19 authored by Hemida, M, Paul HaddadPaul Haddad, Lam, SC, Coates, LJ, Riley, F, Diaz, A, Gooley, AA, Wirth, H-J, Guinness, S, Sekulic, S, Brett PaullBrett Paull
Liquid chromatography (LC) has broad applicability in the pharmaceutical industry, from the early stages of drug discovery to reaction monitoring and process control. However, small footprint, truly portable LC systems have not yet been demonstrated and fully evaluated practically for on-line, in-line or at-line pharmaceutical analysis. Herein, a portable, briefcase-sized capillary LC fitted with a miniature multi-deep UV-LED detector has been developed and interfaced with a portable mass spectrometer for on-site pharmaceutical analysis. With this configuration, the combined small footprint portable LC-UV/MS system was utilized for the determination of small molecule pharmaceuticals and reaction monitoring. The LC-UV/MS system was interfaced directly with a process sample cart and applied to automated pharmaceutical analysis, as well as also being benchmarked against a commercial process UPLC system (Waters PATROL system). The portable system gave low detection limits (∼3 ppb), a wide dynamic range (up to 200 ppm) and was used to confirm the identity of reaction impurities and for studying the kinetics of synthesis. The developed platform showed robust performance for automated process analysis, with less than 5.0% relative standard deviation (RSD) on sample-to-sample reproducibility, and less than 2% carryover between samples. The system has been shown to significantly increase throughput by providing near real-time analysis and to improve understanding of synthetic processes.

History

Publication title

Journal of Chromatography A

Volume

1656

Article number

462545

Number

462545

Pagination

1-10

ISSN

0021-9673

Department/School

Tasmanian Institute of Agriculture (TIA)

Publisher

Elsevier Science Bv

Place of publication

Po Box 211, Amsterdam, Netherlands, 1000 Ae

Rights statement

© 2021 Elsevier B.V. All rights reserved.

Repository Status

  • Restricted

Socio-economic Objectives

Expanding knowledge in the chemical sciences

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