Thioridazine, a Novartis drug withdrawn from the market due to its side effects such as cardiac arrythmias, presents additional drawbacks given by its inherent solid state that allows for the existence of multiple crystalline structures (aka polymorphs) with different pharmacological properties. Ongoing research has shown thioridazine to readily form liquid state compounds such as ionic liquids (ILs) and double salt ionic liquids (DSILs) by combining its cationic form with docusate anion (to increase skin permeability) and lidocaine cation (to combat cardiac arrythmias); these strategies have the potential to improve thioridazine’s bioavailability and remove its polymorphic transformation. Furthermore, the docusate anion allows for thioridazine to be a good candidate for transdermal delivery, as its new structure is much better suited to be delivered through a skin-like membrane into an aqueous environment that mimics blood. Transdermal delivery of thioridazine DSILs will provide an alternate delivery method that is painless and non-invasive. However, an LC-MS methodology for quantifying these drugs in an aqueous environment is still necessary. Here, our focus was on developing a reliable LC-MS method for determining the amount of thioridazine based analytes in a simulated phosphate buffer saline medium which will further allow for assessing the transdermal delivery potential of these compounds.

Assessing the transdermal delivery potential of double salt ionic liquid thioridazine drugs using LC-MS

ACS Spring 2022

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