Effect of pH and Ionic Strength on the Solubility of Quinoline: Back-to-Basics

Abstract

The interest of quinoline as a contaminant agent and as scaffold for the development of new therapeutic agent warrants to revisit the pH-solubility behavior of quinoline (Q) and quinoline derivatives (Q-derivatives) with possible salting-out effect. Q is a weak base with potential hazard upon exposure that may be occupational by inhalation or ingestion of or dermal exposure to particulates in certain industries; or simply by inhalation of cigarette smoke. In contrast, quinoline and its derivatives are useful in diverse therapeutic applications such as anticancer, antiseptic, antipyretic, antiviral, and antimalarial. These claims have raised the possibility of using quinoline motif for the synthesis of new drugs; however, it may act as a pollutant on soil and water as ionizable organic compounds (IOC). The solubility and partitioning behavior of Q may be a critical factor in determining the extent of inhalation and oral absorption or sorption onto soil and water. Studies on the solubility of Q have been reported; however, due to Q-derivatives distinctive usage, it is necessary to revisit and evaluate the solubility profile of Q at different pH levels and ionic strengths. This study reports a simple analytical method for determining the solubility of nitrogen heterocyclic compounds and possible salting-out effect as a function of pH, buffer concentration, and ionic strength. This information can be of value when developing Q-derivatives and to enhance understanding of Q as well as its derivatives behavior in the gastrointestinal tract or when evaluating the presence of Q as an environmental contaminant.

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Acknowledgments

The worked presented herein is the result of a M.S. thesis in the Pharmaceutical Sciences at the College of Pharmacy, University of Arizona. It has never been published but the entire thesis is available on the online repository of the university.

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Correspondence to M. Teresa Carvajal.

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Carvajal, M.T., Yalkowsky, S. Effect of pH and Ionic Strength on the Solubility of Quinoline: Back-to-Basics. AAPS PharmSciTech 20, 124 (2019). https://doi.org/10.1208/s12249-019-1336-9

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KEY WORDS

  • solubility
  • salting-out
  • quinoline
  • ionic strength
  • ionizable organic compounds