High-Throughput Drug Stability Assessment via Biomimetic Metalloporphyrin-Catalyzed Reactions Using Laser-Assisted Rapid Evaporative Ionization Mass Spectrometry (LA-REIMS)

Marton, András; Mohácsi, Zsombor; Decsi, Balázs; Csillag, Balázs; Balog, Júlia; Schäffer, Richard; Karancsi, Tamás; Balogh, György Tibor

doi:10.3390/pharmaceutics16101266

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High-Throughput Drug Stability Assessment via Biomimetic Metalloporphyrin-Catalyzed Reactions Using Laser-Assisted Rapid Evaporative Ionization Mass Spectrometry (LA-REIMS)

by

András Marton

^1,2

,

Zsombor Mohácsi

^3,4

,

Balázs Decsi

¹,

Balázs Csillag

¹,

Júlia Balog

⁵

,

Richard Schäffer

²

,

Tamás Karancsi

^2,6

and

György Tibor Balogh

^1,3,4,*

¹

Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Műegyetem rakpart 3, H-1111 Budapest, Hungary

²

Waters Research Center, H-1031 Budapest, Hungary

³

Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre. u. 9, H-1092 Budapest, Hungary

⁴

Center for Pharmacology and Drug Research & Development, Semmelweis University, Üllői út 26, H-1085, Budapest, Hungary

⁵

Waters Corporation, Cambridge, MA 02142, USA

⁶

Ambimass Kft, Záhony u. 7, H-1031 Budapest, Hungary

^*

Author to whom correspondence should be addressed.

Pharmaceutics 2024, 16(10), 1266; https://doi.org/10.3390/pharmaceutics16101266

Submission received: 30 August 2024 / Revised: 22 September 2024 / Accepted: 25 September 2024 / Published: 27 September 2024

(This article belongs to the Special Issue Current Research in Drug Metabolism and Drug–Drug Interactions (DDIs))

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Abstract

Building extensive drug candidate libraries as early in the development pipeline as possible, with high-throughput in vitro absorption, distribution, metabolism, and excretion (ADME) profiling, is crucial for the selection of lead compounds to guide subsequent research and production phases. Traditionally, the analysis of metabolic stability assays heavily relies on high-throughput LC-MS/MS (liquid chromatography tandem mass spectrometry) techniques to meet with the lead profiling demands. Laser-assisted rapid evaporative ionization mass spectrometry (LA-REIMS) is a quick and efficient technique for characterizing complex biological samples without laborious sample preparation. In this study, using an automated LA-REIMS well plate reader, achieving an 8 s per sample measurement time, the oxidative metabolic stability of active drug agents was assessed using biomimetic metalloporphyrin-based oxidative model reactions. The results obtained using the novel LA-REIMS-based protocol were compared to and corroborated by those obtained using conventional HPLC-UV-MS (high performance liquid chromatography with ultra-violet detection coupled with mass spectrometry) measurements.

Keywords: high-throughput screening; metabolic stability; ambient mass spectrometry; LA-REIMS; biomimetic metalloporphyrin; lead profiling; in vitro models drug metabolism

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MDPI and ACS Style

Marton, A.; Mohácsi, Z.; Decsi, B.; Csillag, B.; Balog, J.; Schäffer, R.; Karancsi, T.; Balogh, G.T. High-Throughput Drug Stability Assessment via Biomimetic Metalloporphyrin-Catalyzed Reactions Using Laser-Assisted Rapid Evaporative Ionization Mass Spectrometry (LA-REIMS). Pharmaceutics 2024, 16, 1266. https://doi.org/10.3390/pharmaceutics16101266

AMA Style

Marton A, Mohácsi Z, Decsi B, Csillag B, Balog J, Schäffer R, Karancsi T, Balogh GT. High-Throughput Drug Stability Assessment via Biomimetic Metalloporphyrin-Catalyzed Reactions Using Laser-Assisted Rapid Evaporative Ionization Mass Spectrometry (LA-REIMS). Pharmaceutics. 2024; 16(10):1266. https://doi.org/10.3390/pharmaceutics16101266

Chicago/Turabian Style

Marton, András, Zsombor Mohácsi, Balázs Decsi, Balázs Csillag, Júlia Balog, Richard Schäffer, Tamás Karancsi, and György Tibor Balogh. 2024. "High-Throughput Drug Stability Assessment via Biomimetic Metalloporphyrin-Catalyzed Reactions Using Laser-Assisted Rapid Evaporative Ionization Mass Spectrometry (LA-REIMS)" Pharmaceutics 16, no. 10: 1266. https://doi.org/10.3390/pharmaceutics16101266

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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High-Throughput Drug Stability Assessment via Biomimetic Metalloporphyrin-Catalyzed Reactions Using Laser-Assisted Rapid Evaporative Ionization Mass Spectrometry (LA-REIMS)

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