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

Citation

Hemida, M and Haddad, PR and Lam, SC and Coates, LJ and Riley, F and Diaz, A and Gooley, AA and Wirth, H-J and Guinness, S and Sekulic, S and Paull, B, Small footprint liquid chromatography-mass spectrometry for pharmaceutical reaction monitoring and automated process analysis, Journal of Chromatography A, 1656 Article 462545. ISSN 0021-9673 (2021) [Refereed Article]


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DOI: doi:10.1016/j.chroma.2021.462545

Abstract

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.

Item Details

Item Type:Refereed Article
Keywords:Miniaturization, Capillary liquid chromatography, Absorbance detectors, Portable mass spectrometry, Process analytical technologies
Research Division:Chemical Sciences
Research Group:Analytical chemistry
Research Field:Separation science
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the chemical sciences
UTAS Author:Hemida, M (Mr Mohamed Hemida)
UTAS Author:Haddad, PR (Professor Paul Haddad)
UTAS Author:Lam, SC (Mr Shing Chung Lam)
UTAS Author:Coates, LJ (Mr Lewellwyn Coates)
UTAS Author:Gooley, AA (Dr Andrew Gooley)
UTAS Author:Wirth, H-J (Dr Hans-Jurgen Wirth)
UTAS Author:Paull, B (Professor Brett Paull)
ID Code:151568
Year Published:2021
Web of Science® Times Cited:1
Deposited By:Plant Science
Deposited On:2022-08-01
Last Modified:2022-08-01
Downloads:0

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