Chiral discrimination of amlodipine from pharmaceutical products using capillary electrophoresis

Melania Cârcu-Dobrin,Gabriel Hancu,Alexandra Georgiana Sabău,Hajnal Kelemen,Lajos Attila Papp,Anca Cârje,Aura Rusu,Gyéresi Árpád

doi:10.1590/s2175-97902019000318259

Melania Cârcu-Dobrin, Gabriel Hancu + Show 6 more

Open Access

https://doi.org/10.1590/s2175-97902019000318259

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Abstract

The present work describes the development of a capillary electrophoresis (CE) method for the chiral discrimination of amlodipine (AML) enantiomers using cyclodextrine (CD) derivatives as chiral selectors. A large number of native and derivatized, neutral and ionized CD derivatives were screened to find the optimal chiral selector; and carboximethyl-β-CD (CM-β-CD) was selected for the enantiomeric discrimination. A factorial analysis study was performed by orthogonal experimental design in which several factors were varied at the same time to optimize the separation method. The optimized method (25 mM phosphate buffer, pH = 9.0, 15 mM CM-β-CD, 15 °C, + 25 kV, 30 mbar/1 second, detection wavelength 230 nm) was successfully applied for the baseline separation of AML enantiomers within 5 minutes. Successful validation and application of the proposed CE method suggest its routine use in enantioselective control of AML in pharmaceutical preparations.

Highlights

Amlodipine (AML) [(RS)-3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl1,4-dihydropyridine-3,5-dicarboxylate] (Figure 1) is a long-acting, dihydropyridine-type inhibitor of the slow calcium channel, used in the treatment of hypertension and angina pectoris
We noticed that the migration time of AML decreases with the increase of the pH value, and AML migrates ahead of the electroosmotic flow (EOF) at pH values above 5.0, its apparent electrophoretic mobility being the sum of its effective electrophoretic mobility and the mobility of EOF
The results show that the optimal result was achieved when using 25 mM phosphate background electrolyte (BGE) at pH 9.0, 15 mM CMβ-CD as chiral selector, 25 kV voltage, 15 °C temperature, mbar/1 second hydrodinamic injection

Summary

Introduction

Amlodipine (AML) [(RS)-3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl1,4-dihydropyridine-3,5-dicarboxylate] (Figure 1) is a long-acting, dihydropyridine-type inhibitor of the slow calcium channel, used in the treatment of hypertension and angina pectoris. AML is a chiral substance and is used in therapy currently as a racemate (Murdoch, Heel, 1992). The two enantiomers, R(+)-AML and S(-)-AML do not have the same pharmaceutical activity; the calcium channel blocking activity and the vasodilatating properties residing primarily in the S(-)-AML enantiomer (Luksa et al, 1997). From the above mentioned facts, it is obvious, that the development of new enantioselective analytical methods are required for pharmacodynamic and pharmacokinetic studies and for the control of enantiomeric composition of pharmaceuticals preparations containing AML

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