Optical Determination of Lithium Levels in Artificial Interstitial Fluid for Treatment Management of Bipolar Disorder

Bipolar Disorder (BD), characterized by mood fluctuating between episodes of mood elevation and depression, is a leading cause of disability worldwide. Lithium continues to be prescribed as a first-line mood stabilizer for the management of BD. However, lithium has a very narrow therapeutic index and it is crucial to carefully monitor lithium plasma levels as concentrations greater than 1.2 mmol/L are potentially toxic and can be fatal. The current techniques of lithium monitoring are cumbersome and require frequent blood tests with the consequent discomfort which results in patients evading treatment. Dermal interstitial fluid (ISF), an underutilized information-rich biofluid, can be a proxy for direct blood sampling and allow lithium drug monitoring as its lithium concentration is proportional to the concentrations in blood. Therefore, in this study we seek to investigate the measurement of lithium therapeutic concentrations in artificial ISF. Our study employs a colorimetric method, based on the reaction between chromogenic agent Quinizarin and Li⁺ ion which can be detected using optical spectroscopy in the visible region (400-800 nm), to determine lithium levels in artificial ISF. The resulting spectra of our experiments show spectral variations which are related to lithium concentrations in spiked samples of artificial ISF, with a correlation coefficient (R) of 0.9. Future work will focus on investigating the feasibility of utilizing ISF for real-time and minimally-invasive lithium drug monitoring.