Chromatographic Analysis of Olopatadine in Hydrophilic Interaction Liquid Chromatography

Abstract

In this paper, chromatographic analysis of active substance olopatadine hydrochloride, which is used in eye drops as antihistaminic agent, and its impurity E isomer by hydrophilic interaction liquid chromatography (HILIC) and application of design of experiments (DoE) methodology are presented. In addition, benzalkonium chloride is very often used as a preservative in eye drops. Therefore, the evaluation of its chromatographic behavior in HILIC was carried out as well. In order to estimate chromatographic behavior and set optimal chromatographic conditions, DoE methodology was applied. After the selection of important chromatographic factors, Box-Behnken design was utilized, and on the basis of the obtained models factor effects were examined. Then, multi-objective robust optimization is performed aiming to obtain chromatographic conditions that comply with several quality criteria simultaneously: adequate and robust separation of critical peak pair and maximum retention of the first eluting peak. The optimal conditions are identified by using grid point search methodology. The experimental verification confirmed the adequacy of the defined optimal conditions. Finally, under optimal chromatographic conditions, the method was validated and applicability of the proposed method was confirmed.

Investigation of olopatadine hydrochloride under stress conditions by hydrophilic interaction liquid chromatography

“…Temperatura kolone podešena je na 30 °C, a brzina protoka mobilne faze na 1 mL min -1 . Volumen injektovanja bio je 20 μL, a talasna dužina detekcije 257 nm [12].…”

“…Olopatadin-hidrohlorid tretitan je različitim stres agensima, kao što su kiselina, baza, oksidaciono sredstvo i povišena temperatura. Stepen degradacije pod uticajem različitih stres agenasa praćen je HILIC metodom [12].…”

“…Mehanizmi razdvajanja u HILIC su veoma kompleksni i podrazumevaju kombinaciju particije i adsorpcije analita, kao i jonske interakcije analita sa negativno naelektrisanim silanilnim grupama [29]. Kako je ponašanje olopatadinhidrohlorida u HILIC-u opisano u referenci [12], očekivano je da se u posmatranom sistemu mogu pratiti degradacioni proizvodi različite polarnosti i time dobiti novi podaci o stabilnosti olopatadin-hidrohlorida. U ovom istraživanju, olopatadin-hidrohlorid najpre je tretiran bazom, odnosno 0,5 i 1 M NaOH.…”

“…Cilj ovog rada je izvođenje studija forsirane degradacije na olopatadin-hidrohloridu i praćenje nastalih proizvoda degradacije metodom tečne hromatografije hidrofilnih interakcija (eng. Hidrophilic Interaction Liquid Chromatography -HILIC) opisanom u radu [12]. Pored toga, cilj je bio i određivanje kinetika degradacije kako bi se izračunale odgovarajuće konstante brzine i poluvremena razgradnje u kiseloj, baznoj sredini, kao i nakon izlaganja oksidacionom sredstvu.…”

Isolation and Characterization Photo Degradation Impurities of Drug Product Olopatadine Hydrochloride by Spectral Techniques

“…HCl [2] Since the impurity profile study of any pharmaceutical substance is a crucial part of process development, it was felt necessary to develop a reliable, High-Performance Liquid Chromatography method for identification and quantitative determination of impurities in Olopatadine Hydrochloride. [3][4] During force degradation studies, two unknown degradation impurities were detected in photodegradation of Olopatadine Hydrochloride, using a newly developed gradient reversed-phase High-performance liquid chromatography method. [5][6].…”