A Chitosan-Carbon Nanotube-Modified Microelectrode for In Situ Detection of Blood Levels of the Antipsychotic Clozapine in a Finger-Pricked Sample Volume

Adv Healthc Mater. 2019 Aug;8(15):e1900462. doi: 10.1002/adhm.201900462. Epub 2019 Jun 26.

Abstract

The antipsychotic clozapine is the most effective medication available for schizophrenia and it is the only antipsychotic with a known efficacious clinical range. However, it is dramatically underutilized due to the inability to test clozapine blood levels in finger-pricked patients' samples. This prevents obtaining immediate blood levels information, resulting in suboptimal treatment. The development of an electrochemical microsensor is presented, which enables, for the first time, clozapine detection in microliters volume whole blood. The sensor is based on a microelectrode modified with micrometer-thick biopolymer chitosan encapsulating carbon nanotubes. The developed sensor detects clozapine oxidation current, in the presence of other electroactive species in the blood, which generate overlapping electrochemical signals. Clozapine detection, characterized in whole blood from healthy volunteers, displays a sensitivity of 32 ± 3.0 µA cm-2 µmol-1 L and a limit-of-detection of 0.5 ± 0.03 µmol L-1 . Finally, the developed sensor displays a reproducible electrochemical signal (0.6% relative standard deviation) and high storage stability (9.8% relative standard deviation after 8 days) in serum samples and high repeatability (9% relative standard deviation for the 5th repetition) in whole blood samples. By enabling the rapid and minimally invasive clozapine detection at the point-of-care, an optimal schizophrenia treatment is provided.

Keywords: antipsychotic clozapine; chitosan-carbon nanotube-modified microelectrodes; electrochemical sensors; finger-pricked blood tests; therapeutic drug monitoring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biosensing Techniques / methods*
  • Chitosan / chemistry*
  • Clozapine / blood*
  • Clozapine / therapeutic use
  • Electrochemical Techniques
  • Humans
  • Limit of Detection
  • Microelectrodes
  • Nanotubes, Carbon / chemistry*
  • Oxidation-Reduction
  • Schizophrenia / drug therapy
  • Schizophrenia / pathology

Substances

  • Nanotubes, Carbon
  • Chitosan
  • Clozapine