Quinidine and quinine based double salt ionic liquids

Abstract

Injury caused by medications is the leading cause of death in the United States. Drug induced liver injury is any form of liver injury caused by primary or alternative medication. A potential solution to prevent liver injury is the pairing of these drugs into one single compound in liquid form: an active pharmaceutical ingredient (API) and an FDA approved compound, or two APIs, can be combined in their cationic or anionic form into a single ionic compound leading to the formation of new dual active APIs in liquid form (aka ionic liquids that melt below body temperature). These newly formed liquid drugs are able to retain the pharmaceutical properties of the original APIs. Moreover, the combination of three or more drugs into a single ionic compound, namely a double salt ionic liquid would allow one to add additional properties (such as transdermal delivery) to the final liquid drug. Our research focuses on applying the ionic liquids strategies to quinidine (QD) and quinine (QN), two drugs known to cause liver injury, by pairing them with drugs that offer liver protection properties (e.g., N-acetyl-L-cysteine or NALC) and with compounds that will increase their transdermal permeability (e.g., sodium docusate or NaDoc). Here we show the synthesis and spectroscopic characterization of new double salt ionic compounds obtained by combining QD or QN cations with NALC and Doc
anions in different cation to anion molar ratios.