Comparison of Various Chromatographic Systems for Identification of Vortioxetine in Bulk Drug Substance, Human Serum, Saliva, and Urine Samples by HPLC-DAD and LC-QTOF-MS.

Anna Petruczynik,Tomasz Tuzimski,Dariusz Juchnowicz,Karol Wróblewski,Krzysztof Wojtanowski,Hanna Karakuła-Juchnowicz,Tomasz Mroczek

doi:10.3390/molecules25112483

Anna Petruczynik, Tomasz Tuzimski + Show 5 more

Open Access

https://doi.org/10.3390/molecules25112483

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Abstract

Background: Determination of psychotropic drugs in clinical study is significant, and the establishment of methodologies for these drugs in biological matrices is essential for patients’ safety. The search for new methods for their detection is one of the most important challenges of modern scientific research. The methods for analyzing of psychotropic drugs and their metabolites in different biological samples should be based on combining a very efficient separation technique including high-performance liquid chromatography (HPLC), with a sensitive detection method and effectively sample preparation methods. Objective: Retention, peaks symmetry and system efficiency of vortioxetine on Hydro RP, Polar RP, HILIC A (with silica stationary phase), HILIC-B (with aminopropyl stationary phase), and ACE HILIC-N (with polyhydroxy stationary phase and SCX columns were investigated. Various mobile phases containing methanol or acetonitrile as organic modifiers and different additives were also applied to obtained optimal retention, peaks shape, and systems efficiency. The best chromatographic procedure was used for simultaneous analysis of vortioxetine and its metabolites in human serum, urine and saliva samples. Methods: Analysis of vortioxetine was performed in various chromatographic systems: Reversed phase (RP) systems on alkylbonded or phenyl stationary phases, hydrophilic interaction liquid chromatography (HILIC), and ion-exchange chromatography (IEC). Based on the dependence of log k vs the concentration of the organic modifier, log kw values for vortioxetine in various chromatographic systems were determined and compared with calculated log P values. Solid phase extraction (SPE) method was applied for sample pre-treatment before HPLC analysis. HPLC-QTOF-MS method was applied for confirmation of presence of vortioxetine and some its metabolites in biological samples collected from psychiatric patient. Conclusions: Differences were observed in retention parameters with a change of the applied chromatographic system. The various properties of stationary phases resulted in differences in vortioxetine retention, systems’ efficiency, and peaks’ shape. Lipophilicity parameters were also determined using different HPLC conditions. The most optimal systems were chosen for the analysis of vortioxetine in biological samples. Both serum and urine or saliva samples collected from patients treated with vortioxetine can be used for the drug determination. For the first time, vortioxetine was detected in patient’s saliva. Obtained results indicate on possibility of application of saliva samples, which collection are non-invasive and painless, for determination and therapeutic drug monitoring in patients.

Highlights

Major depressive disorder is a main cause of disability and is associated with significant reductions in quality of life, have a negative effect on productivity, reduced overall health and significant economic costs
Vortioxetine standard was chromatographed on different columns in various eluent systems for choose the optimal chromatographic systems for analysis of the compound in biological samples
Tested chromatographic systems were compared in terms of retention of vortioxetine, peak shape and system efficiency (Table 1)

Summary

Introduction

Major depressive disorder is a main cause of disability and is associated with significant reductions in quality of life, have a negative effect on productivity, reduced overall health and significant economic costs. The most frequently used pharmacological treatments for major depressive disorder include the selective serotonin reuptake inhibitors and the serotonin and norepinephrine reuptake inhibitors [1] These drugs can may generate only a limited antidepressant response, improved responses have been obtained with different or combined therapies involving additional mechanisms, such as the allosteric serotonin reuptake inhibitor escitalopram or by combinations of medications. The methods for analyzing of psychotropic drugs and their metabolites in different biological samples should be based on combining a very efficient separation technique including high-performance liquid chromatography (HPLC), with a sensitive detection method and effectively sample preparation methods. Various mobile phases containing methanol or acetonitrile as organic modifiers and different additives were applied to obtained optimal retention, peaks shape, and systems efficiency.

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Conclusion