A semi-automated, isotope-dilution high-resolution mass spectrometry assay for therapeutic drug monitoring of antidepressants

用于抗抑郁药治疗药物监测的半自动化同位素稀释高分辨率质谱分析

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作者:Johanna M Lindner, Michael Vogeser, Katharina Sorg, Stefanie H Grimm

Background

Therapeutic drug monitoring (TDM) of antidepressants is important to ensure compliance and to rule out pharmacokinetic abnormalities. Therefore, reliable

Conclusions

We have established a selective method for the quantification of antidepressants with outstanding precision using a high-resolution Orbitrap mass spectrometer. The applicability of HRMS instruments to TDM was demonstrated.

Methods

After manual protein precipitation of serum samples, further sample clean-up was achieved using a Turbo Flow column preconnected to the analytical LC column. Stable isotope-labelled counterparts of the target analytes were used as internal standards. For detection, we used a Q Exactive Focus Orbitrap mass spectrometer operating in full-scan mode. Ionization was performed in positive ESI.

Results

Accuracy, recovery, and matrix effect were acceptable for all analytes. The method demonstrated outstanding precision (within-run imprecision <4.5%, between-run imprecision <7.5%). The selectivity of the method was ensured by chromatographic separation of all isobaric compounds. Close agreement between Orbitrap and triple stage based quantification was observed in a comparison measurement of leftover patient samples. Conclusions: We have established a selective method for the quantification of antidepressants with outstanding precision using a high-resolution Orbitrap mass spectrometer. The applicability of HRMS instruments to TDM was demonstrated.

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