Electrochemical study of the catechol-modified chitosan system for clozapine treatment monitoring.

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TitleElectrochemical study of the catechol-modified chitosan system for clozapine treatment monitoring.
Publication TypeJournal Article
Year of Publication2014
AuthorsWinkler, TE, Ben-Yoav, H, Chocron, SE, Kim, E, Kelly, DL, Payne, GF, Ghodssi, R
JournalLangmuir
Volume30
Issue48
Pagination14686-93
Date Published2014 Dec 9
ISSN1520-5827
Abstract<p>This work presents a thorough electrochemical and reliability analysis of a sensing scheme for the antipsychotic clozapine. We have previously demonstrated a novel detection approach for this redox-active drug, highly effective in schizophrenia treatment, based on a catechol-modified chitosan film. The biomaterial film enables amplification of the oxidative current generated by clozapine through redox cycling. Here, we study critical electrochemical and material aspects of the redox cycling system to overcome barriers in point-of-care monitoring in complex biological samples. Specifically, we explore the electrochemical parameter space, showing that enhanced sensing performance depends on the presence of a reducing mediator as well as the electrochemical technique applied. These factors account for up to 1.75-fold and 2.47-fold signal enhancement, respectively. Looking at potential interferents, we illustrate that the redox cycling system allows for differentiation between selected redox-active species, clozapine's structurally largely analogous metabolite norclozapine as well as the representative catecholamine dopamine. Furthermore, we investigate material stability and fouling with reuse as well as storage. We find no evidence of film fouling due to clozapine; slow overall biomaterial degradation with successive use accounts for a 2.2% absolute signal loss and can be controlled for. Storage of the redox cycling system appears feasible over weeks when kept in solution with only 0.26%/day clozapine signal degradation, while ambient air exposure of three or more days reduces performance by 58%. This study not only advances our understanding of the catechol-modified chitosan system, but also further establishes the viability of applying it toward sensing clozapine in a clinical setting. Such point-of-care monitoring will allow for broader use of clozapine by increasing convenience to patients as well as medical professionals, thus improving the lives of people affected by schizophrenia through personalized medicine.</p>
DOI10.1021/la503529k
Alternate JournalLangmuir
PubMed ID25383917