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Chromatographic retention behaviour, modelling and separation optimisation of the quaternary ammonium salt isometamidium chloride and related compounds on a range of reversed-phase liquid chromatographic stationary phases

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Abstract

This paper describes the reversed-phase liquid chromatographic behaviour of the trypanocidal quaternary ammonium salt isometamidium chloride and its related compounds on a range of liquid chromatographic phases possessing alkyl and phenyl ligands on the same inert silica. In a parallel study with various extended polar selectivity phases which possessed different hydrophobic/silanophilic (hydrogen bonding) activity ratios, the chromatographic retention/selectivities of the quaternary ammonium salts was shown to be due to a co-operative mechanism between hydrophobic and silanophilic interactions. The highly aromatic and planar isometamidium compounds were found to be substantially retained on stationary phases containing aromatic functionality via strong π–π interactions. The chemometric approach of principal component analysis was used to characterise the chromatographic behaviour of the isometamidium compounds on the differing phases and to help identify the dominant retention mechanism(s). Two-dimensional (temperature/gradient) retention modelling was employed to develop and optimise a rapid liquid chromatography method for the separation of the six quaternary ammonium salts within 2.5 min which would be suitable for bioanalysis using liquid chromatography–mass spectrometry. This is the first reported systematic study of the relationship between stationary phase chemistries and retention/selectivity for a group of quaternary ammonium salts.

Structure of isometamidium and related quaternary ammonium salts and their LC separation on a diverse range of RP columns.

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Acknowledgment

Merial SAS (Lyon, France) for supplying the ISM commercial samples.

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Author notes

  1. Justice N. A. Tettey

    Present address: Laboratory and Scientific Section, Policy Analysis and Research Branch, Division for Policy Analysis and Public Affairs, United Nations Office on Drugs and Crime, Room E-1577, P.O. Box 500, 1400, Vienna, Austria

Authors and Affiliations

  1. Strathclyde Institute for Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, UK

    Gesa J. Schad, Graham G. Skellern & Justice N. A. Tettey

  2. 1 The Markham Centre, Hichrom Ltd, Station Road, Theale, Reading, Berkshire, RG7 4PE, UK

    Melvin R. Euerby

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  1. Gesa J. Schad
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  2. Melvin R. Euerby
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  3. Graham G. Skellern
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  4. Justice N. A. Tettey
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Correspondence to Melvin R. Euerby.

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Schad, G.J., Euerby, M.R., Skellern, G.G. et al. Chromatographic retention behaviour, modelling and separation optimisation of the quaternary ammonium salt isometamidium chloride and related compounds on a range of reversed-phase liquid chromatographic stationary phases. Anal Bioanal Chem 404, 239–255 (2012). https://doi.org/10.1007/s00216-012-6105-5

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  • DOI: https://doi.org/10.1007/s00216-012-6105-5

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