Deep eutectic solvents as green and sustainable diluents in headspace gas chromatography for the determination of trace level genotoxic impurities in pharmaceuticals

Abbasi, Nabeel Mujtaba; Anderson, Jared L.; Pellett, Jackson D.; Yehl, Peter M.; del Barrio, Mary-Anne; Zhong, Qiqing

doi:10.1016/j.jpba.2024.116128

Title: Deep eutectic solvents as green and sustainable diluents in headspace gas chromatography for the determination of trace level genotoxic impurities in pharmaceuticals

Journal Article · Thu Mar 28 00:00:00 UTC 2024 · Journal of Pharmaceutical & Biomedical Analysis

DOI: https://doi.org/10.1016/j.jpba.2024.116128 · OSTI ID:2382784

Abbasi, Nabeel Mujtaba ^[1]; Anderson, Jared L. ^[2]; Pellett, Jackson D. ^[1]; Yehl, Peter M. ^[1]; del Barrio, Mary-Anne ^[1]; Zhong, Qiqing ^[1]

Genentech, South San Francisco, CA (United States)
Iowa State Univ., Ames, IA (United States); Ames Laboratory (AMES), Ames, IA (United States)

Genotoxic impurities (GTIs) are potential carcinogens that need to be controlled down to ppm or lower concentration levels in pharmaceuticals under strict regulations. The static headspace gas chromatography (HS-GC) coupled with electron capture detection (ECD) is an effective approach to monitor halogenated and nitroaromatic genotoxins. Deep eutectic solvents (DESs) possess tunable physico-chemical properties and low vapor pressure for HS-GC methods. In this study, zwitterionic and non-ionic DESs have been used for the first time to develop and validate a sensitive analytical method for the analysis of 24 genotoxins at sub-ppm concentrations. Compared to non-ionic diluents, zwitterionic DESs produced exceptional analytical performance and the betaine: 7 (1,4- butane diol) DES outperformed the betaine: 5 (1,4-butane diol) DES. Limits of detection (LOD) down to the 5-ppb concentration level were achieved in DESs. Wide linear ranges spanning over 5 orders of magnitude (0.005–100 µg g^–1) were obtained for most analytes with exceptional sensitivities and high precision. The method accuracy and precision were validated using 3 commercially available drug substances and excellent recoveries were obtained. Finally, this study broadens the applicability of HS-GC in the determination of less volatile GTIs by establishing DESs as viable diluent substitutes for organic solvents in routine pharmaceutical analysis.

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Research Organization:: Ames Laboratory (AMES), Ames, IA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division (CSGB)

Grant/Contract Number:: AC02-07CH11358

OSTI ID:: 2382784

Report Number(s):: IS-J--11,352

Journal Information:: Journal of Pharmaceutical & Biomedical Analysis, Journal Name: Journal of Pharmaceutical & Biomedical Analysis Vol. 244; ISSN 0731-7085

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
deep eutectic solvents
genotoxic impurities
headspace gas chromatography
ionic liquids
pharmaceutical analysis
separations

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