Determination of Mesalamine Related Impurities from Drug Product by Reversed Phase Validated UPLC Method

Trivedi Rakshit Kanubhai,Kharkar Amit R,Patel Mukesh C

doi:10.1155/2011/382137

Trivedi Rakshit Kanubhai, Kharkar Amit R + Show 1 more

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https://doi.org/10.1155/2011/382137

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Abstract

In the present study gradient reversed-phase UPLC method was developed for simultaneous determination and separation of impurities and degradation products from drug product. The chromatographic separation was performed on acquity UPLC BEH C18 column (50 mm×2.1 mm, 1.7 µm) using gradient elution. Other UPLC parameters which were optimised are flow rate, 0.7 mL/min; detection wavelength, 220 nm; column oven temperature, 40°C and injection volume 7 µL. Stability indicating capability was established by forced degradation experiments and separation of known degradation products. The method was validated as per International Conference on Harmonization (ICH) guideline. For all impurities and mesalamine, LOQ (limit of quantification) value was found precise with RSD (related standard daviation) of less than 2.0%. In essence, the present study provides an improved low detection limit and lower run time for evaluation of pharmaceutical quality of mesalamine delayed-release formulation. Moreover, the developed method was successfully applied for quantification of impurities and degradation products in mesalamine delayed-release formulation. The same method can also be used for determination of related substances from mesalamine drug substance.

Highlights

Mesalamine (5-aminosalicylic acid, 5-ASA), the therapeutically active moiety of sulfasalazine[1,2,3] is routinely employed in the treatment of inflammatory bowel disease, that is ulcerative colitis and Crohn’s disease
The important criteria for development of successful RP-UPLC method for determination of mesalamine related substances in delayed-release tablets were: the method should be able to determine all impurities of the drug in single run with the good amount of resolution and it should be accurate, reproducible, robust, stability indicating, free from interference and straightforward enough for routine use in quality control laboratory
To develop the stability indicating method, first the retention behaviour of these all compounds with change in percentage of organic solvent and with change in buffer substances and change in pH of buffer was studied on Waters Acquity BEH C18 column (50 mm x 2.1 mm, 1.7 μm). 1-Octane sulphonic acid ion pair reagent was used in buffer preparation to improve the resolution and avoid the other substances co elution at same retention time in RP chromatography

Summary

Introduction

Mesalamine (5-aminosalicylic acid, 5-ASA), the therapeutically active moiety of sulfasalazine[1,2,3] is routinely employed in the treatment of inflammatory bowel disease, that is ulcerative colitis and Crohn’s disease. Various types of formulations are available for the mesalamine[4]. Administrated mesalamine is rapidly and almost completely absorbed from the small intestine[5,6,7]. Mesalamine drug profile[10] and degradation mechanism in aqueous solution was reported[11]. Several articles for mesalamine metabolism[12,13] and its determination by HPLC14-16 and HPLC-ESI-MS/MS17 has been reported. Estimation of mesalamine and its metabolites in plasma and urine by HPLC18-20 and by fluorescence detector[21] are reported. Mesalamine HPLC determination in rectal tissue biopsies[22] and endoscopic intestinal biopsy in human has been reported[23]. Identification of unknown impurity in mesalamine was reported[24,25]

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