Rapid Simultaneous Determination of Fourteen Antidepressants and Thirteen 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.

BACKGROUND A comprehensive, stable, and efficient high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed for rapidly analyzing 14 antidepressants and 13 antipsychotics in human plasma for routine clinical therapeutic drug monitoring (TDM). 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 min. 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 correlation coefficient of r ≥ 0.99. The method was accurate and precise with acceptable intra- and interday precisions (coefficients of variation, ≤20 % for lower limit of quantification and ≤15 % for other quality control samples) and accuracy of 85.51-114.77 %. This analysis method has been completely validated and successfully utilized in routine clinical TDM for more than 9963 samples [including 488 samples having drug concentrations above the laboratory alert level (supra-alert level samples)] at Xiamen Xianyue Hospital. CONCLUSION 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.