Rapid Simultaneous Determination of 14 Antidepressants and 13 Antipsychotics in Human Plasma by Using High-Performance Liquid Chromatography-Tandem Mass Spectrometry With Dynamic Multiple Reaction Monitoring and Its Application to Therapeutic Drug Monitoring

Ther Drug Monit. 2021 Aug 1;43(4):577-588. doi: 10.1097/FTD.0000000000000839.

Abstract

Background: A comprehensive, stable, and efficient high-performance liquid chromatography-tandem mass spectrometry method was developed for rapidly analyzing 14 antidepressants and 13 antipsychotics in human plasma for routine clinical therapeutic drug monitoring.

Methods: Simple protein precipitation was used for the pretreatment of plasma samples; dynamic multiple reaction monitoring was used to avoid the loss of sensitivity caused by numerous ion transitions. In all, 80 ion transitions of 40 compounds were quantitatively determined in 6 minutes.

Results: The limit of detection for the 27 analytes was in the range of 0.1-30 ng/mL, and all calibration lines prepared using blank plasma were linear with a correlation coefficient of r2 ≥ 0.99. The method was accurate and precise with acceptable intraday and interday precisions (coefficients of variation, ≤20% for a lower limit of quantification and ≤15% for other quality control samples) and an accuracy of 85.51%-114.77%. This analysis method has been completely validated and successfully used in routine clinical therapeutic drug monitoring for more than 9963 samples [including 488 samples having drug concentrations above the laboratory alert level (supra-alert-level samples)] at Xiamen Xianyue Hospital.

Conclusions: This dynamic method is comprehensive (includes most antidepressants and antipsychotics listed in China), reliable (stably used for almost 2 years), and efficient (convenient sample processing and short run time) and provides a large amount of meaningful data for optimized pharmacotherapy. Our experimental data from the plasma concentrations of supra-alert-level samples could serve as a reference for the interpretation of the pharmacokinetics of patients with a high risk of toxicity or loss of tolerability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents* / blood
  • Antidepressive Agents* / pharmacokinetics
  • Antipsychotic Agents* / blood
  • Antipsychotic Agents* / pharmacokinetics
  • Chromatography, High Pressure Liquid
  • Drug Monitoring*
  • Humans
  • Reproducibility of Results
  • Tandem Mass Spectrometry

Substances

  • Antidepressive Agents
  • Antipsychotic Agents