Trace Extraction of Metoprolol from Plasma, Urine and EBC Samples Using Modified Magnetic Nanoparticles Followed by Spectrofluorimetric Determination for Drug Monitoring Purposes

Abstract

Background: Metoprolol is a selective β1-adrenergic receptor antagonist (β-blockers). It is widely used for the treatment of hypertension and other related diseases. Metoprolol can be used as a doping agent in sports, thus has been included in the list of forbidden drugs. In Iran, therapeutic drug monitoring (TDM) of β-blockers is an applied procedure in some cases. A therapeutic regimen could be easily managed by the determination of drug levels in biological fluids which is a relatively costly process and requires highly skilled technical staff. Using a simple and low-cost analytical procedure may help to use TDM in routine clinical practice. Methods: A real biological sample was prepared and its pH was adjusted to 3-4, then metoprolol was quickly extracted using magnetic iron oxide nanoparticles (MIONPs) modified by sodium dodecyl sulfate (SDS) and determined by applying spectrofluorimetry at 340 ± 3 nm after excitation at 283 ± 3 nm. Results: The extraction and determination conditions including, the amount of MIONPs and SDS, pH of the solution, standing time, desorption solvent type and volume were investigated and adjusted. Calibration curves were linear over the concentration range of 6–100 ng/mL for plasma and 5–100 ng/mL for water, urine and exhaled breath condensate samples, respectively. Intra and inter-day precision values for determination of metoprolol in different samples were less than 5.6 % and 6 %, respectively, and accuracy (as a relative error) was better than 5 %. Moreover, standard addition recovery tests were carried out, and the analytical recoveries ranged from 86 % to 113 %. The limits of detection (LOD) and limits of quantification (LOQ) of metoprolol were found to be in the range of 2.1-3.4 ng/mL and 6.3- 10.2 ng/mL, respectively. Conclusion: The developed method was successfully applied to biological samples taken from a volunteer who was given an oral tablet of 50 mg metoprolol.