Simultaneous determination of four serotonin selective reuptake inhibitors by an UPLC MS-MS method with clinical application in therapeutic drug monitoring
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An analytical method of ultra-high performance liquid chromatography coupled to tandem mass spectrometry detection was developed and validated for the simultaneous quantification in plasma of four selective serotonin reuptake inhibitor antidepressants: sertraline, escitalopram, paroxetine, fluoxetine, and its metabolite norfluoxetine. A simple protein precipitation was performed with acetonitrile containing 100 ng/mL of indomethacin, which was used as internal standard. Chromatographic separation was carried out on an Acquity BEH C18 column with isocratic elution of the mobile phase consisting of 5 mmol/L ammonium acetate with 0.1%25 formic acid (A) and acetonitrile (B) at a 60:40 proportion, respectively. The flow rate was 0.4 mL/min with a run time of 5 min. A positive electrospray ionization source was used for detection. The method was linear in a range of 5-800 ng/mL, with determination coefficients greater than 0.991. The accuracy ranged from 91%25 to 112%25 for intra-assay and from 89%25 to 112%25 for inter-assay. The variation coefficients ranged from 3.1%25 to 14.88%25 for intra-assay and from 3.60%25 to 14.74%25 for inter-assay precision. The method was successfully applied for the analysis of 73 samples from patients under treatment with these antidepressants; 36.9%25 of the samples had concentrations outside therapeutic ranges. This method can be applied for routine analysis in clinical practice, simplifying sample processing, reducing analysis time and consequently the costs associated with it. © 2022 Elsevier B.V.
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Antidepressants; Isocratic elution; Method validation; SSRI; Therapeutic drug monitoring; UPLC-MS/MS Drug products; Electrospray ionization; High performance liquid chromatography; Mass spectrometry; Metabolites; Patient monitoring; Patient treatment; Analytical method; Antidepressant; Clinical application; Isocratic elution; Method validations; Simultaneous determinations; SSRI; Therapeutic drug monitoring; Ultra-high performance liquid chromatographies; UPLC-MS/MS; Acetonitrile; acetonitrile; antidepressant agent; clonazepam; enalapril; escitalopram; fluoxetine; folic acid; indometacin; levothyroxine; metformin; norfluoxetine; olanzapine; paroxetine; pregabalin; quetiapine; risperidone; serotonin uptake inhibitor; sertraline; adult; aged; analytical parameters; Article; behavior disorder; carryover effect; chemical procedures; chemical structure; clinical practice; drug determination; drug monitoring; drug stability; dysthymia; electrospray; female; generalized anxiety disorder; human; ICD-10; limit of quantitation; linearity; liquid chromatography-mass spectrometry; major clinical study; major depression; male; mass spectrometry; matrix effect; measurement accuracy; measurement precision; mental disease; multiple reaction monitoring; protein precipitation; quality control; retention time (chromatography); schizophrenia; selectivity; social phobia; substance use; ultra performance liquid chromatography; validation process
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