PhD Scientific Days 2024

Pharmaceutical Sciences and Health Technologies I.

The Development of a Dual Cyclodextrin Capillary Electrophoresis System for the Separation of Tolperisone and its Degradation Products

Előadó neve

Lakatos, Péter, PhD

Előadó munkahelye

Department of Pharmacodynamics, Semmelweis University

Előadó telefonszáma

+36206169231

Előadó e-mail címe

lakatos.peter5@gmail.com

Az előadás címe

The Development of a Dual Cyclodextrin Capillary Electrophoresis System for the Separation of Tolperisone and its Degradation Products

Szerző(k) neve és munkahelye

Péter Lakatos¹, Zsuzsanna Ignáth¹, Tamás Tábi¹, Éva Szökő¹

1: Department of Pharmacodynamics, Semmelweis University

Bemutatás módja

Szóbeli

Szekció

Pharmaceutical Sciences and Health Technologies I.

Language of the presentation

English

Preferred session

Pharmaceutical Sciences and Health Technologies

Összefoglaló szövege

Introduction: The clinical safety of the centrally acting muscle relaxant tolperisone has been recently reassessed due to rare but severe allergic reactions that reportedly occur during its use. It has been suggested that reactive degradation products of tolperisone may be responsible for this side effect and that their formation is determined by the composition of pills.
Aims: Identification of degradation products with potential allergenic properties in tolperisone preparations and development of a capillary electrophoresis (CE) method for the separation of tolperisone enantiomers and their most common degradants.
Method: Measurements were carried out using silica capillaries (40/50 cm) in a lithium acetate (LiAc) buffer under a field strength of 500 V/cm. Proper separation of analytes was achieved by a dual cyclodextrin system containing carboxymethyl-beta-cyclodextrin (CMBCD) and beta-cyclodextrin (BCD). Molecules were detected based on their UV absorption.
Results: Stability tests showed excessive degradation of tolperisone to 1-(4-methylphenyl)propan-1-one (MMPO) and 2-methyl-1-(4-methylphenyl)prop-2-en-1-ol (MMP) in alkaline conditions (0.1M NaOH), which was confirmed by mass spectrometry. Tolperisone enantiomers, MMPO and MMP were separated using 25 mM LiAc buffer (pH 5.0) and 8 mM CMBCD. As migration of these impurities present in pills in trace amounts ahead of tolperisone peaks is preferred for their detection, 3 mM BCD was added to the separation buffer. BCD was found to form selective complexes with MMP and MMPO, increasing their velocity and thus modifying the migration of order of analytes, which allowed the detection of both major degradants in the presence of high concentration tolperisone. Next, the presence of impurities was examined in two tolperisone preparations of different Hungarian manufacturers past their date of expiry. MMP was detected in only one of the preparations suggesting the importance of pill composition in the degradation profile.
Conclusion: A dual cyclodextrin CE method was developed and validated for the quantification of the most common degradation products of tolperisone. The difference in MMP content of pills suggests that the selection of appropriate excipients can prevent the formation of this potentially allergenic degradation product making tolperisone preparations significantly safer.
Funding: ÚNKP-23-4-I-SE-21

University

Semmelweis University

Supervisor

Prof. Éva Szökő

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6121

Start

17:30

End

17:40