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

• Published in: Clinica chimica acta 2018-10, Vol.485, p.243-257
• Main Authors: Degreef, Maarten, van Nuijs, Alexander L.N., Maudens, Kristof E.
• Format: Article
• Language: English
• Subjects: Antidepressant; Liquid chromatography-tandem mass spectrometry; Therapeutic drug monitoring; Triple quadrupole
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2018.06.047

Antidepressant (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). A 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. The 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. The 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. [Display omitted] •Simultaneous quantitative analysis of 40 antidepressants or metabolites.•Simple and fast sample preparation/chromatography.•Wide calibration range from sub-therapeutic to toxic levels.•Applicable to both therapeutic drug monitoring and forensic case work.