Abstract: Objective To establish an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of trazodone concentrations in serum of patients that can be used for clinical individualized medications with trazodone. Methods The chromatographic column was MSCB-2A (2.1 mm × 50 mm, 2.5μm). The mobile phase consisted of methanol (B) -water (A, containing 0.01 % ammonia) under gradient elution (the gradient set at 0~0.2 min, 55 % B; 0.2~2.0 min, 55 %~95 % B; 2.0~-2.5 min, 95 %~95 % B; 2.5~2.6 min, 95 %~55 % B; 2. 6~3. 0 min, 55 %~55 % B). The flow rate was 0.5 mL·min^{- 1}, the column temperature 40℃, and the injection volume 0.1 μL in a positive ion mode. The serum was precipitated by acetonitrile, and diazepam was used as the internal standard. The specificity, standard curve and lower limit of quantification, precision and recovery, matrix effect, and stability of the method were investigated. Meanwhile, this method was applied to the determination of blood concentrations of 16 patients using trazodone, and the test results were analyzed before intervention opinions were given. Results The linear range of trazodone in serum was 10.0 to 1 500.0 ng·mL^-1 (R² = 0.9994). The relative standard deviation (RSD) of intra-day and inter-day precision of low, medium, and high quality control concentration samples (50.0, 400.0, 1 000.0 ng·mL^-1) was less than 7%, and the accuracy ranged from 91.90% to 98.67%. The serum with low, medium, and high concentrations of trazodone remained stable at room temperature for 4 h, for 24 h in a 2 to 8℃ refrigerator, after long-term freezing of 3 months or repeated freeze-thaw cycles. The accuracy ranged from 95.04% to 105.78% under varied conditions. The method was also applied to the therapeutic drug monitoring of clinical samples of trazodone. Conclusion This UPLC-MS/MS method is rapid, simple, stable, accurate, highly sensitive, and almost pollution-free in the detection of plasma concentrations of trazodone This method has been successfully applied to the clinical individualized medication of trazodone.

Key words: trazodone, UPLC-MS/MS, therapeutic drug monitoring, blood drug concentration, human serum, individualized medication