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Immobilized Artificial Membrane Chromatography Using Acetonitrile-Rich Mobile Phase for Comparison of Retention Properties Between Phospholipidosis-Inducing and Non-inducing Basic Drugs

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Abstract

Immobilized artificial membrane chromatography has been reported providing a rough estimation of phospholipidosis induction risk of drugs. Unfortunately, however, the accurate assessment of basic drugs remains a challenge. In this study, we aimed to evaluate the hydrophobic interactions and ionic/polar interactions between a basic drug and an immobilized artificial membrane to clearly discriminate between phospholipidosis inducers and non-inducers. The retention of 14 model basic drugs was determined using mobile phases with varying acetonitrile contents. The Van’t Hoff plot using an acetonitrile-rich mobile phase revealed that most of the inducers showed biphasic retention, whereas the retention of non-inducers was monophasic. Then, effect of the ionic/polar interactions on the discrimination between DIPL inducers and non-inducers was then studied. For this aim, salts concentration was increased in the acetonitrile-rich mobile phase. No significant difference was observed between chlorpromazine (inducer) and pindolol (non-inducer) as the model drugs. We then compared the acetonitrile concentration when the dominant interaction was shifted from the reversed phase retention to the ionic/polar interactions. We found that the acetonitrile levels when the dominant interaction of the inducers shifted from the hydrophobic interaction to the ionic/polar interactions were higher than those of non-induces. In addition, at the optimized acetonitrile content, the inducers and non-inducers can be correctly discriminated. Shift of the dominant interaction in retention to the immobilized artificial membrane shows a possibility as a novel tool for the risk prediction of phospholipidogenisity.

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Data availability statement

The data that supports the findings of this study are available within the article and its supplementary material.

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Authors and Affiliations

  1. School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women’s University, Koshien-Kyubancho, 11-68, Nishinomiya, Hyogo, Japan

    Yoshie Iwakuma, Haruka Okamoto, Ryohei Hamaguchi & Yukihiro Kuroda

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  1. Yoshie Iwakuma
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  2. Haruka Okamoto
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All authors contributed to the study conception and design. All authors read and approved the final manuscript.

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Iwakuma, Y., Okamoto, H., Hamaguchi, R. et al. Immobilized Artificial Membrane Chromatography Using Acetonitrile-Rich Mobile Phase for Comparison of Retention Properties Between Phospholipidosis-Inducing and Non-inducing Basic Drugs. Chromatographia 86, 43–54 (2023). https://doi.org/10.1007/s10337-022-04225-0

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