Original Article

Stability-indicating LC Method for Quantification of Azelnidipine: Synthesis and Characterization of Oxidative Degradation Product

10.4274/tjps.galenos.2020.76753

  • Sandeep S Sonawane
  • Pooja C Bankar
  • sanjay kshirsagar

Received Date: 15.09.2020 Accepted Date: 21.12.2020 Turk J Pharm Sci 0;0(0):0-0 [e-Pub]

Objectives:

In the work presented here, the degradation behavior of azelnidipine under diversified forced degradation conditions was studied. A stability-indicating liquid chromatographic method was established which could separate and resolve azelnidipine from its degradation products. Further, chemical kinetics under acid and alkali conditions were studied and validation studies were performed.

Materials and Methods:

Using reversed-phase chromatography, azelnidipine and its formed degradants were resolved using phosphate buffer (pH 3.0) and methanol in a mixture of 10:90 % v/v as a mobile phase at a flow rate of 1.0 mL/min. All eluents were detected at a wavelength of 256 nm.

Results:

Azelnidipine was degraded under acid, alkali, wet heat, and oxidized environment. The pH-dependent rate of hydrolysis of azelnidipine under acidic and alkaline conditions was studied and chemical kinetics were determined. Further, the oxidative degradation product of azelnidipine was synthesized and characterized as 3-(1-Benzhydrylazetidin-3-yl) 5-isopropyl 2-amino-6-methyl-4-(3-nitrophenyl) pyridine-3,5-dicarboxylate (dehydro-AZD).

Conclusions:

The susceptibility of azelnidipine to hydrolysis was associated with the presence of ester at 3 and 5 positions of 1,4 dihydropyridine. Further, under oxidative conditions, the aromatization of 1,4 dihydropyrinine could form dehydro-AZD. Azelnidipine follows the first-order reaction under acid and alkali hydrolysis and found more susceptible to degrade under acidic conditions. The synthesized and confirmed dehydro-AZD was found as one of the metabolites and impurities of azelnidipine.

The evaluated validation parameters ascertained the practicality of the method for the quantification of azelnidipine tablets.

Keywords: azelnidipine, chemical kinetics, degradation product, HPLC, method validation, stability-indicating