Development of a Stability-Indicating RP-HPLC Method for Determination of Rupatadine and its Degradation Products in Solid Oral Dosage Form

Harshal Kanubhai Trivedi

doi:10.3797/scipharm.1208-10

Abstract

A simple, sensitive, and reproducible reversed-phase high-performance liquid chromatography (RP-HPLC) method, coupled with a photodiode array detector, was developed for the determination of rupatadine (RUPA) and its related substances in pharmaceutical dosage forms. Chromatographic separation was achieved on the Hypersil BDS (150 x 4.6 mm, 5 μm) column with a mobile phase containing a gradient mixture of a buffer (acetate buffer pH-6.0) and solvent (methanol). The eluted compounds were monitored at 264 nm for the related substances and assay, the flow rate was 1.0 mL/min, and the column oven temperature was maintained at 50°C. The developed method separated RUPA from its four known and three unknown impurities within 15.0 min. Rupatadine was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal, and photolytic degradation. Rupatadine was found to degrade significantly under oxidative stress conditions, and degrade slightly under acid, base, hydrolytic, thermal, and photolytic stress conditions. All impurities were well-resolved from each other and from the main peak, showing the stability-indicating power of the method. The developed method was validated as per the International Conference on Harmonization (ICH) guidelines. The developed and validated RP-HPLC method is LC-MS compatible and can be explored for the identification of eluted unknown impurities of RUPA.

Highlights

Rupatadine fumarate (RUPAF) is 8-chloro-11-{1-[(5-methylpyridin-3-yl)methyl]piperidin-4-ylidene}-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (2E)-but-2-enedioate.RUPAF discovery, pre-clinical, and clinical development was performed by J
The spiked solution of RUPA (1000 μg/mL), IMP-A (5 μg/mL), IMP-B (5 μg/mL), Imp-C (5 μg/mL), Imp-D (5 μg/mL), and fumaric acid was subjected to separation by reversed-phase high-performance liquid chromatography (RP-high-performance liquid chromatography (HPLC))
Various types of mobile phase-A (MP-A) and mobile phase-B (MP-B) were studied to optimize the method, which are summarized in Table 1 with the associated observations

Summary

Introduction

Rupatadine fumarate (RUPAF) is 8-chloro-11-{1-[(5-methylpyridin-3-yl)methyl]piperidin-4-ylidene}-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (2E)-but-2-enedioate.RUPAF discovery, pre-clinical, and clinical development was performed by J. There is no stability-indicating HPLC/UPLC method reported in the literature for the determination of RUPA and its impurities in solid oral dosage form. Felt necessary to develop a new rapid, stability-indicating method for the determination of the assay and impurities in RUPA solid oral dosage form.

Results

Conclusion