Amorim, CG

Araujo, AN

Gil, Renato

Sarraguça, Mafalda

Portuguese

Repositório Aberto da Universidade do Porto

   CPH9  Health Lithium determination in human serum with improved accuracy using potentiometric detection R. Gil, M.C. Sarraguça, C.G. Amorim, M.C.B.S.M. Montenegro, A.N. Araújo LAQV-REQUIMTE/Departamento de Ciências Químicas, Faculdade de Farmácia – Universidade do Porto, R. Jorge Viterbo Ferreira, 228. 4050-313 Porto, Portugal. Email: renatogil19@gmail.com  Lithium salts have been widely and effectively used as psychotherapeutic drugs in the treatment of bipolar disorders for more than 50 years. However, lithium requires careful determination of the correct dose for every patient because its levels are affected by each individual’s metabolism and must be maintained within a relative narrow therapeutic range (0.5 – 1.2 mmol L-1)1. An overdose of lithium causes irreversible damage in the nervous system and kidneys and, in the other hand, a lithium level below the curable dose make the treatment ineffective. Therefore, lithium monitoring in blood serum has a critical and vital importance. Concerning this purpose, different analytical methods have been reported, namely atomic absorption spectrometry, flame emission photometry and potentiometry1. Potentiometry based in ion-selective electrodes (ISEs) is widely used to perform billions of assays, mainly in clinical diagnosis through determination of electrolytes in biological fluids. ISEs allows simple measurements with inexpensive instrumentation and provide rapid results. However, for determination of lithium ions in blood serum, potentiometric sensors suffer from lack of selectivity towards sodium ions, since it is found naturally in human serum at quite high level (135 – 150 mmol L-1)2. Therefore, researchers have been still focusing on the developments of highly sensitive and selective lithium electrodes. In this work, a lithium ISE based on a liquid polymeric membrane that contains lithium ionophore VIII and bis(butylpentyl)adipate (BBPA) as solvent mediator was successfully tested in flow injection analysis, presenting a linear slope of 53mV decade-1 down to 0.1 mmol L-1. To overcome the low selectivity in the presence of sodium ions at physiological levels, a new approach based on the chemometric relationship between these two ions was tested. A quadratic 5-level D-optimal design was used with two variables (concentration of lithium and sodium ions) and one response (lithium signal, in mV) in a total of 15 experiments. Multiple linear regression (MLR) was used to correlate the potentiometric response with the independent variables. The model goodness-of-fit was evaluated using analysis of variance (ANOVA) at a 95% of confidence level, which include Q2 that is a measure of how the model will predict the responses for new experimental conditions, and R2 that is the percent variation of the response explained by the model. To validate the model, 13 independent experiments were used.  The model demonstrated a good prediction ability and a good correlation between the lithium concentration and the potentiometric signal, even in the presence of physiological sodium levels. The model has been tested through the analysis of spiked human serum in three levels of lithium concentration (below, within and above of therapeutic range) after a simple protein precipitation protocol. The results were quite promising because the method allowed determination of lithium in the post-spiked samples with great accuracy. However, the protein precipitation protocol should be improved in order to determine the lithium levels in the pre-spiked samples with great accuracy. Future approaches include the determination of lithium levels in real samples from patients under treatment with lithium salts as well as the development of a simple electrochemical device for easily monitoring the lithium levels in order to minimise any risk of harm to the body.  Acknowledgements: We thank the Fundação para a Ciência e Tecnologia for financial support (SFRH/BD/131504/2017). The work was also supported by UID/QUI/50006/2019 with funding from FCT/MCTES through national funds.  References:  1. Kamenica M.; Kothur R. R.; Willows A.; Patel B. A.; Cragg P. G. Sensors (Basel). 2017, 17, 2430. 2. Gadzekpo V. P. Y.; Moody G. J.; Thomas J. D. R. Analyst. 1986, 111, 567. 99

Lithium determination in human serum with improved accuracy using potentiometric detection

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Lithium determination in human serum with improved accuracy using potentiometric detection

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