Optical determination of lithium therapeutic levels in micro-volumes of interstitial fluid.

BACKGROUND

Long-term management of bipolar disorder (BD), characterized by mood fluctuating between episodes of mania and depression, involves the regular taking of lithium preparations as the most reliable mood stabilizer for bipolar patients. However, despite its effectiveness in preventing and reducing mood swings and suicidality, lithium has a very narrow therapeutic index and it is crucial to carefully monitor lithium plasma levels as concentrations >1.2 mmol/L are potentially toxic and can be fatal. Current methods of lithium therapeutic monitoring involve frequent blood tests, which have several drawbacks related to the invasiveness of the technique, comfort, cost and reliability. Dermal interstitial fluid (ISF) is an accessible and information-rich biofluid, and correlations have been found between blood and ISF levels of lithium medication.

METHODS

In the current study, we sought to investigate the optical determination of lithium therapeutic concentrations in samples of ISF extracted from porcine skin utilizing a microneedle-based approach. Monitoring of lithium levels in porcine ISF was achieved by employing a spectrophotometric method based on the reaction between the chromogenic agent Quinizarin and lithium.

RESULTS

The resulting spectra show spectral variations which relate to lithium concentrations of lithium in samples of porcine ISF with a coefficient of determination (R2 ) of 0.9. This study has demonstrated successfully that therapeutic levels of lithium in micro-volumes of porcine ISF can be measured with a high level of accuracy utilizing spectroscopic techniques.

CONCLUSIONS

The results support the future development of a miniaturized and minimally-invasive device for lithium monitoring in bipolar patients.