Validation of a simple, fast liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of 40 antidepressant drugs or their metabolites in plasma

Abstract

IntroductionAntidepressant (AD) use has increased significantly over the last decades. Therapeutic drug monitoring is recommended for compliance, toxicity and treatment efficiency. ADs also show a high prevalence in forensic cases. Few methods have been developed that combine a fast, easy sample clean-up with a quantification based on liquid chromatography-triple quadrupole mass spectrometry (LC-QQQ). MethodologyA liquid-liquid extraction (LLE) was performed using 200 μL of plasma. The evaporated and reconstituted upper fraction was injected on a LC-QQQ system monitoring 3 transitions per compound. The method was fully validated according to international guidelines. Results & discussionThe chromatographic run time was under 12 min. The LLE was successful in removing interferences with minimal sensitivity loss. Calibration curves ranged from sub-therapeutic to toxic concentrations. Quality control samples showed high accuracy (81%–119%) and precision (≤14%) within and between batches. Stability was tested at ambient temperature and −20 °C. The method was successfully applied to external quality control and case samples. ConclusionThe presented method successfully quantifies 40 compounds of interest. Because of a simple sample clean-up, a relatively short chromatographic run and a wide calibration range this method can be implemented in therapeutic drug monitoring, forensic research and related fields.