A rapid and fully-automated method for the quantitation of tricyclic antidepressants in serum using turbulent-flow liquid chromatography-tandem mass spectrometry.

Abstract Background We describe a fully-automated turbulent-flow liquid chromatography–tandem mass spectrometry method for the detection of tricyclic antidepressant drugs (amitriptyline, desipramine, imipramine, and nortriptyline) in serum. Methods Human serum and an internal standard were injected directly onto a Cyclone-P online solid-phase extraction (SPE) column (0.5 × 50 mm). Following removal of serum proteins and other components the analytes were transferred to a Hypersil Gold C-18 (50 × 3 mm) analytical column. Elution occurred with a gradient of water and acetonitrile each with 0.1% formic acid. Analytes were ionized and detected over a 3.5 min analysis time by electrospray-ionization mass spectrometry with selected reaction monitoring (SRM). Matrix effects were well-characterized and carryover, precision, linearity, recovery and limits of detection and quantitation were evaluated. Results The simple and complex precision CVs for all compounds were ≤ 16%. The limits of detection and quantitation for all drugs were ≤ 3 ng/ml and  0.96. Proficiency testing materials had values within 2 SDI of peer group means for all drugs. Conclusion Based on validation data, this is a specific, sensitive fully-automated method for rapid quantitation of tricyclic antidepressants in serum.