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

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.

Application of capillary zone electrophoresis to determine second-generation H1 antihistaminic drugs, loratadine and rupatadine

“…There are different methods to identify and quantify LOR and RUP in pharmaceutical preparations and biological tissue. LOR (El Ragehy, Badawey, Khateeb, 2002;Rupérez, Fernández, Barbas, 2002;Radhakrishna et al, 2003;Ulavapalli et al, 2011) and RUP (Nogueira et al, 2008;Trivedi, Patel, 2012) were determined or quantified by HPLC. Capillary electrophoresis (CE) was also used as a method to determine LOR (Rambla-Alegre et al, 2010;El-Awady, Belal, Pyell, 2013;Hancu et al, 2014) and RUP (Nogueira et al, 2008).…”

Green micellar stability‐indicating high‐performance liquid chromatography method for determination of rupatadine fumarate in the presence of its main impurity desloratadine: Oxidative degradation kinetics study

“…Several analytical methods have been reported for RUP determination either alone or in combination with other drugs. such as spectrophotometry [6][7][8][9][10], spectrofluorimetry [11,12], HPTLC [13][14][15], micellar electrokinetic chromatography [16], and HPLC methods [17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Several stability-indicating assay methods have been reported for RUP determination as summarized in Table S1.…”

“…Literature review revealed that most reported HPLC methods for RUP determination incorporate more than one organic modifier with a very high organic % that reaches 90% v/v in some methods [17–19, 21, 23, 25, 26, 28–30]. Some methods use heptane sulfonic acid for RUP ion pairing [27], and some use polar cyano‐column [29]or less nonpolar C8 column [17] or incorporate gradient elution with increasing organic ratio within the run [20, 24].…”

Resonance Rayleigh scattering and spectrofluorimetric approaches for the selective determination of rupatadine using erythrosin B as a probe: application to content uniformity test

“…[ 8–12 ] Conversely, several chromatographic methods with various detection patterns have been reported to determine rupatadine. [ 13–24 ] Chromatographic techniques require large volumes of hazardous organic solvents, tedious procedures, sometimes need expensive detectors and have lengthy procedures. Spectroscopic techniques are frequently used in laboratories to characterize or quantify medicines.…”