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Comprehensive Stress Degradation Studies of Fipronil: Identification and Characterization of Major Degradation Products of Fipronil Including Their Degradation Pathways Using High Resolution-LCMS

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Abstract

Fipronil belongs to the phenylpyrazole family of insecticides and functions by interrupting the γ-aminobutyric acid system and chloride ion channels of pests. Studies have shown Fipronil can undergo several degradation pathways in the environment to form degradants that may be toxic to non-target aquatic life. In this study, a comprehensive forced degradation study of Fipronil was carried out following ICH guidelines to generate, characterize, and identify the major degradation products of Fipronil. Stress conditions included acidic, alkaline, oxidative, thermal (solid and solution states), and photolytic (solid and solution states). Separation of six major degradation products (DPs) was achieved using reversed phase high-performance liquid chromatography (HPLC) with gradient elution. The DPs were characterized and identified using HPLC-high-resolution mass spectrometry (HPLC-HRMS) and comparison of tandem MS/MS fragmentation profiles. The Fipronil dimer required isolation through semi-preparative HPLC and analysis by nuclear magnetic resonance (NMR) to elucidate and confirm its structure. The proposed structures of DPs were based upon the given degradation pathways of Fipronil. The key results and findings of this study will provide better understanding of Fipronil stability and its major degradation products including degradation/formation pathways, which would assist designing of more stable Fipronil formulations and finished products with extended shelf-life including enhanced efficacy with decreased adverse effects.

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Acknowledgements

The authors would like to thank all the analytical scientists in the Global Pharmaceutical Technical Support (GPTS) group at BIAH North Brunswick Research Center and to the dedicated analytical team (of GPTS) in Pharmaron laboratory for their support and execution of various studies described in this paper.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Boehringer Ingelheim Animal Health USA Inc. (BIAH), 631 US Route 1 South, North Brunswick, NJ, 08902, USA

    Shane N. Berger & Abu M. Rustum

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  1. Shane N. Berger
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  2. Abu M. Rustum
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Contributions

A.M.R. conceptualization, experimental design, manuscript review/editing. S.N.B. data collection, data analysis, manuscript preparation, manuscript editing.

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Correspondence to Shane N. Berger.

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The authors’ affiliated company, Boehringer Ingelheim Animal Health (BIAH) USA Inc. approved the submission of this manuscript.

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Berger, S.N., Rustum, A.M. Comprehensive Stress Degradation Studies of Fipronil: Identification and Characterization of Major Degradation Products of Fipronil Including Their Degradation Pathways Using High Resolution-LCMS. Chromatographia 87, 249–257 (2024). https://doi.org/10.1007/s10337-024-04324-0

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