Reliable clinical serum analysis with reusable electrochemical sensor: Toward point-of-care measurement of the antipsychotic medication clozapine

Biosens Bioelectron. 2017 Sep 15;95:55-59. doi: 10.1016/j.bios.2017.04.008. Epub 2017 Apr 12.

Abstract

Clozapine is one of the most promising medications for managing schizophrenia but it is under-utilized because of the challenges of maintaining serum levels in a safe therapeutic range (1-3μM). Timely measurement of serum clozapine levels has been identified as a barrier to the broader use of clozapine, which is however challenging due to the complexity of serum samples. We demonstrate a robust and reusable electrochemical sensor with graphene-chitosan composite for rapidly measuring serum levels of clozapine. Our electrochemical measurements in clinical serum from clozapine-treated and clozapine-untreated schizophrenia groups are well correlated to centralized laboratory analysis for the readily detected uric acid and for the clozapine which is present at 100-fold lower concentration. The benefits of our electrochemical measurement approach for serum clozapine monitoring are: (i) rapid measurement (≈20min) without serum pretreatment; (ii) appropriate selectivity and sensitivity (limit of detection 0.7μM); (iii) reusability of an electrode over several weeks; and (iv) rapid reliability testing to detect common error-causing problems. This simple and rapid electrochemical approach for serum clozapine measurements should provide clinicians with the timely point-of-care information required to adjust dosages and personalize the management of schizophrenia.

Keywords: Clozapine; Electrochemical sensor; Electrodeposition; Graphene; Serum; Therapeutic drug monitoring.

MeSH terms

  • Antipsychotic Agents / blood*
  • Antipsychotic Agents / therapeutic use
  • Biosensing Techniques*
  • Chitosan / chemistry
  • Clozapine / blood*
  • Clozapine / therapeutic use
  • Graphite / chemistry
  • Humans
  • Point-of-Care Systems
  • Schizophrenia / blood
  • Schizophrenia / drug therapy

Substances

  • Antipsychotic Agents
  • Graphite
  • Chitosan
  • Clozapine