Juvenile rat and pediatric trazodone studies: how to gain extra sensitivity to overcome bioanalytical challenges

Bioanalysis. 2019 Jan;11(1):21-32. doi: 10.4155/bio-2018-0236. Epub 2018 Dec 10.

Abstract

Aim: Trazodone (TZD) is used for the treatment of depression in adults and, off-label, as a sleep medication in adult and pediatric populations. The off-label use is well documented, however further clinical studies are needed to confirm its efficacy and safety for the treatment of sleep disorders. In this scenario, we developed a bioanalytical method to quantify low TZD concentrations in samples collected by capillary microsampling (CMS) to support dose finding, Good Laboratory Practice juvenile rat toxicokinetic and upcoming pediatric studies.

Methodology: A method using only 8 μl of plasma was developed and successfully used for analyzing CMS samples from juvenile rats throughout toxicokinetic study.

Conclusion: By harmoniously maximizing each analytical step, we achieved a sensitive method to quantify TZD in CMS samples.

Keywords: CMS; LC–MS/MS; capillary microsampling; juvenile rats; toxicokinetic study; trazodone.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / administration & dosage
  • Anti-Anxiety Agents / blood*
  • Blood Specimen Collection / instrumentation
  • Blood Specimen Collection / methods*
  • Calibration
  • Capillaries
  • Chromatography, Liquid
  • Dose-Response Relationship, Drug
  • Female
  • Male
  • Rats
  • Reference Standards
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry
  • Toxicokinetics
  • Trazodone / administration & dosage
  • Trazodone / blood*

Substances

  • Anti-Anxiety Agents
  • Trazodone