Quantification of mirtazapine in tablets via DNA binding mechanism; development of a new HPLC method

Ecem Kuzpınar, Abdullah Al Faysal, Pelin Şenel, Taner Erdoğan, Ayşegül Gölcü*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Atypical antidepressant mirtazapine (MIR) is mostly prescribed for the management of major depressive disorder. The identification of MIR in pharmaceutical dosage forms was made possible by developing a novel, quick, sensitive high-performance liquid chromatography (HPLC) approach that was verified in accordance with ICH recommendations. In the first part of this study, HPLC investigations were optimized with regard to variables including pH, working column, mobile phase, temperature, and flow rate. The limit of detection (LOD) was 0.013 ppm, the limit of quantification (LOQ) was 0.044 ppm, and the linear range was computed as 0.5–15 ppm (R2 = 0.9998). The recovery investigation assessed the method's accuracy, which was shown to range between 98.82 and 100.97 %. In the second part, by using UV–vis spectroscopy, HPLC, thermal denaturation, and viscosity measurements, the mechanism of binding interaction of MIR with double-stranded fish sperm deoxyribonucleic acid (dsDNA) has been thoroughly studied. The DNA binding constants (Kb) were determined using UV–Vis absorption and HPLC methods. To investigate the interactions of MIR with dsDNA, molecular docking calculations and additionally, molecular dynamics simulations were performed. Results showed that MIR is located in the minor groove of dsDNA, and in addition to hydrogen bonding, electrostatic interaction is also formed between the aromatic ring of MIR and phosphate oxygen of dsDNA. Finally, a binding characterization study using MIR tablets was also conducted in order to assess the interaction mechanism of the DNA with the drug using the validated analytical procedure developed for the MIR molecule.

Original languageEnglish
Article number124019
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume1234
DOIs
Publication statusPublished - 15 Feb 2024

Bibliographical note

Publisher Copyright:
© 2024

Funding

The authors would like to thank the support of the grant of Istanbul Technical University (Scientific Research Projects Unit) under TYL-2019-42362 project. The computational studies reported in this paper were partially performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources) and Kocaeli University.

FundersFunder number
TUBITAK ULAKBIM
Kocaeli Üniversitesi
Istanbul Teknik ÜniversitesiTYL-2019-42362

    Keywords

    • Drug quantification
    • dsDNA
    • Groove binding
    • HPLC
    • Mirtazapine
    • Molecular docking

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