Simple and Accurate Quantitative Analysis of 16 Antipsychotics and Antidepressants in Human Plasma by Ultrafast High-Performance Liquid Chromatography/Tandem Mass Spectrometry

Background:In psychopharmacology, treatment with psychotropic drugs is often suboptimal, mainly because of the high interindividual variability in pharmacokinetic properties. Therapeutic drug monitoring (TDM) can be a valuable tool for monitoring the individual effects of a prescribed dosage in a patient, and it facilitates antipsychotic treatment by increasing the effectiveness and safety of drugs and by reducing treatment costs. The aim of this study was to develop and validate an ultrafast liquid chromatography (UFLC) method with tandem mass spectrometric detection for the measurement of 16 antipsychotics and antidepressants in human plasma samples for TDM or other applications.Methods:The method was developed to replace traditional methods using the solid-phase extraction of proteins precipitated with methanol/acetonitrile containing 0.1% formic acid. Quantitative analysis was performed by UFLC combined with a tandem mass spectrometer using a Synergy 3u-Hydro-RP (2.0 x 50 mm, 3 m) column with a mobile phase consisting of 0.1% formic acid and acetonitrile.Results:A simple, fast, and sensitive UFLC-tandem mass spectrometry method for the simultaneous measurement of commonly used antipsychotics (aripiprazole, chlorpromazine, paliperidone, quetiapine, risperidone, ziprasidone, clozapine, and olanzapine), antidepressants (citalopram, escitalopram, mirtazapine, fluoxetine, paroxetine, sertraline, venlafaxine plus O-desmethylvenlafaxine, and fluvoxamine) and an antidementia drug (donepezil) has been developed. The total run time of the chromatographic separation was 6.0 minutes. The precision and accuracy varied from 0.90% to 14% and from 88.5% to 118%, respectively. A 6-point standard curve covering the clinically relevant ranges with a power function fit was applied for calibration. Ion suppression due to matrix effects and the internal standards were investigated. Their recoveries varied from 89% to 110%.Conclusions:This new validated method fulfills all criteria for TDM and was successfully applied in the routine TDM of antipsychotics and antidepressants at the First Affiliated Hospital of Kunming Medical University.