Stability-Indicating High-Performance Liquid Chromatography Method for Determination of Antihistamine Drug Azelastine

Abstract

Objective: The objective of this research was to develop a simple, precise, accurate, and stability-indicating reverse-phase high-performance liquid chromatographic method for estimation of azelastine hydrochloride (AZL) in nasal spray preparation. Methods:Chromatography was performed on a 250 mm×4.6 mm, 5-μm particle size, Waters Spherisorb CN column using (50:50 v/v) mixture of potassium dihydrogen phosphate buffer and acetonitrile as mobile phase. The detection was carried out at 290 nm and flow rate employed was 1.0 ml/min. The degradation of AZL was studied under different ICH recommended stress conditions. Results:The retention time was 4.34 min for AZL. Linearity was established in the concentration range of 5-120 µg/ml, with a correlation coefficient of 0.9996. Limit of detection (LOD) and limit of quantitation (LOQ) were found to be 0.81 µg/ml and 2.44 µg/ml, respectively. Percentage recovery was found between 99 and 102%. The values of percentage relative standard deviation (<2%) proved the high precision of the proposed method. The method was found to be robust regarding any small variation in the column temperature, pH of mobile phase, and mobile phase ratio. AZL was found stable in 5 M HCl at 80°C for 5 h, 5 M NaOH at 80°C for 5 h, 30% H 2 O 2 at 80°C for 5 h, and in oven at 70°C for 8 h. Conclusion:The results obtained in this research work clearly proved that the proposed HPLC method for the assay of AZL in nasal spray preparation is simple, precise, specific, accurate, and stability indicating. It indicates that the method is suitable for analysis of AZL in the raw material and the pharmaceutical product without interference from excipients.

Chemical Stability Study of H1 Antihistaminic Drugs from the First and the Second Generations, Diphenhydramine, Azelastine and Bepotastine, in Pure APIs and in the Presence of Two Excipients, Citric Acid and Polyvinyl Alcohol

“…However, its sensitivity to thermal stress was to some extent different. Our study confirmed its higher stability in a strong acidic medium, which is consistent with previously reported results [ 19 ]. What is more, AZE was stable in a strong alkaline medium ( Table 2 ).…”

“…In addition, some visible changes were observed in the UV spectrum of AZE after irradiation in solutions of pH 10–13, where the maximum of photodegradation of AZE (>90%) was observed ( Figure 5 B). These data were in agreement with previously reported results from the literature confirming the photosensitivity of AZE in methanolic solution [ 19 ]. At the same time, it was interesting to observe that AZE was shown to be more sensitive to UV/VIS irradiation than to high temperatures at similar pH conditions.…”

“…As far as previous reports from the literature are concerned, one stability-indicating HPLC method for the determination of AZE and one HPLC method for separation of AZE from its degradation products has been reported. In addition, the structures of two degradants under acidic and alkaline (DP1), and oxidative (DP2) conditions have been proposed [ 19 , 20 ]. The HPLC method with gradient elution has also been reported for the separation of AZE and Impurities B, D and E [ 21 ].…”

“…When it comes to the photostability of DIPH, AZE and BEPO, the literary resources are even more limited. In a few studies [ 13 , 15 , 17 , 19 , 20 , 22 , 23 , 24 ], these drugs were exposed to artificial UV light or natural sunlight, in solid state, solutions and liquid formulations, but the breadth of these experiments was rather scarce, and no kinetic aspects were taken into account. Only one paper from the literature presented the experiments on BEPO photostability and proposed the possible structures of its five degradation products (DP2–DP6) [ 26 ].…”

Factorial design-assisted reverse phase HPLC–UV approach for the concurrent estimation of cetirizine and azelastine in aqueous humor

“…The developed HPLC procedure, whose mobile phase is made up of only two components, is much simpler than other documented HPLC procedures 14 , 15 , 30 , 31 , whose mobile phases are made up of three or more components, therefore requiring more time for preconditioning. Also, our procedure had a lower LOQ for both drugs than the documented procedures 13 – 16 , 28 , 29 . All of these previous methods were developed by changing one factor at a time, which has assured to be time-consuming, expensive, does not fix errors, and may yield unpredictable responses 45 .…”