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HOLLOW-FIBER LIQUID PHASE MICROEXTRACTION FOR DETERMINATION OF FLUOXETINE IN HUMAN SERUM BY NANO-LIQUID CHROMATOGRAPHY COUPLED TO HIGH RESOLUTION MASS SPECTROMETRY
Fluoxetine
Drug Monitoring
Mass Spectrometry
Chromatography, Liquid
Autor
Afiliación
Universidade Federal do Paraná. Departamento de Química. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Mass Spectrometry Facility - RPT02H. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Mass Spectrometry Facility - RPT02H. Curitiba, PR, Brasil.
Universidade Federal do Paraná. Departamento de Química. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Mass Spectrometry Facility - RPT02H. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Mass Spectrometry Facility - RPT02H. Curitiba, PR, Brasil.
Universidade Federal do Paraná. Departamento de Química. Curitiba, PR, Brasil.
Resumen en ingles
Therapeutic drug monitoring (TDM) is a personalized care tool based on the determination of a target drug concentration in human serum. An antidepressant drug of interest for such investigations is fluoxetine (FXT), due to a severe impact of genetic polymorphisms on its metabolism. A bioanalytical method employed for TDM purposes must exhibit satisfactory selectivity and detectability, which becomes more difficult due to highly complex biological matrices. In this study, a highly selective bioanalytical method for the determination of FXT in human serum is proposed, which provides excellent clean-up efficiency based on a low cost hollow fiber liquid-phase microextraction (HF-LPME) sample preparation step and nano-liquid chromatography coupled to high-resolution mass spectrometry (nano-LC-HRMS). HF-LPME was performed using a two-phase “U” configuration, with 6 cm fiber, 20 μL of 1-octanol acting as supported liquid membrane, and ammonium hydroxide (pH 10) as the donor phase with NaCl (10 % m/v) and methanol (5 % v/v) as additives, requiring only 250 μL of the sample. The procedure was conducted for 30 min under a 750 rpm stirring rate. Gradient elution was carried out employing an acetonitrile–water as a mobile phase, the composition of 30:70 to 100:00 (v/v) for 15 min, using formic acid 0.1 % (v/v) as an additive. MS1 was acquired in an Orbitrap mass analyzer, while MS2 was acquired in a linear trap quadrupole. Satisfactory linearity (Pearson’s r = 0.99709) was obtained for a concentration range of 0.02 to 2.5 μg mL 1, which is compatible with the therapeutic and toxic range for FXT. The developed method presents adequate precision (1.61 to 7.45 %) and accuracy (95 to 114 %) and allows the dilution of high concentration samples in a 1:4 ratio (v/v), enabling its application for forensic serum samples. To our knowledge, this is the first study reporting a method based on HF-LPME and nano-LC-HRMS with any analytical purpose, especially with a TDM focus.
Palabras clave en portugues
Soro humanoPalabras clave en ingles
Human serumFluoxetine
Drug Monitoring
Mass Spectrometry
Chromatography, Liquid
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