Stress Degradation Studies on Varenicline Tartrate and Development of a Validated Stability-Indicating HPLC Method

Sudhakar S Pujeri

doi:10.3797/scipharm.1109-22

Abstract

A simple, rapid and stability-indicating reversed-phase liquid chromatographic method was developed for the assay of varenicline tartrate (VRT) in the presence of its degradation products generated from forced decomposition studies. The HPLC separation was achieved on a C18 Inertsil column (250 mm × 4.6 mm i.d. particle size is 5 μm) employing a mobile phase consisting of ammonium acetate buffer containing trifluoroacetic acid (0.02M; pH 4) and acetonitrile in gradient program mode with a flow rate of 1.0 mL min−1. The UV detector was operated at 237 nm while column temperature was maintained at 40 °C. The developed method was validated as per ICH guidelines with respect to specificity, linearity, precision, accuracy, robustness and limit of quantification. The method was found to be simple, specific, precise and accurate. Selectivity of the proposed method was validated by subjecting the stock solution of VRT to acidic, basic, photolysis, oxidative and thermal degradation. The calibration curve was found to be linear in the concentration range of 0.1–192 μg mL−1 (R2 = 0.9994). The peaks of degradation products did not interfere with that of pure VRT. The utility of the developed method was examined by analyzing the tablets containing VRT. The results of analysis were subjected to statistical analysis.

Highlights

Varenicline (VRT) chemically known as (6R,10S)-7,8,9,10-tetrahydro-6H-6,10-methanopyrazino[2,3-h][3]benzazepine 2,3-dihydroxybutanedioate (1:1 salt, Fig. 1) was approved by US FDA as an aid to smoking cessation treatment [1,2,3,4,5,6]
We have developed a sensitive HPLC method that overcomes the above limitations for quantitative determination of varenicline tartrate (VRT) in bulk sample and formulations
The developed HPLC method revealed that there was no interference from the impurities, degradation products and excipients to determine the assay of drug substance in pure and pharmaceutical formulation

Summary

Introduction

Varenicline (VRT) chemically known as (6R,10S)-7,8,9,10-tetrahydro-6H-6,10-methanopyrazino[2,3-h][3]benzazepine 2,3-dihydroxybutanedioate (1:1 salt, Fig. 1) was approved by US FDA as an aid to smoking cessation treatment [1,2,3,4,5,6]. The solution stability of VRT in the assay method was carried out by leaving both the test solutions of the sample and reference standard in tightly capped volumetric flasks separately, at room temperature, up to the study period of 48 h. The mobile phase stability was carried out by assaying the freshly prepared bulk drug and formulation sample solutions against freshly prepared reference standard solution with an interval of 8 h.

Results

Conclusion