Evaluation of Pharmaceutical Quality of Mesalamine Delayed Release Tablets Using a New High Sensitivity Reversed-Phase UPLC Method for its Genotoxic/Aniline Impurity

Rakshit Kanubhai Trivedi,Mukesh C Patel

doi:10.1155/2011/953235

Abstract

A reversed phase ultra performance liquid chromatography (UPLC) method was developed and validated for the quantification of aniline in mesalamine delayed-release tablets. The optimization of the experimental condition was carried out considering some important requirements like, detection limit, short run time and reproducibility. In the present study, isocratic reversed-phase UPLC method was developed for determination and separation of aniline from the drug product. The drug and impurity are well separated by using a reversed phase (Reprosil Gold C18-XBD) column and mobile phase comprising of buffer pH 6.0 and acetonitrile in the ratio of 90:10 v/v. Other UPLC parameters which were optimised are flow rate, 0.5 mL/min; detection wavelength, 200 nm; column oven temperature, 50°C and injection volume 7 µL. Stability indicating capability was also established by forced degradation experiments. The method was validated as per ICH guideline. LOQ (limit of quantification) concentration (18 ng/mL) was found precise with RSD of less than 2%. 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 also successfully applied for quantification of aniline in mesalamine delayed-release formulation. The same method can also be used for determination of aniline from drug substances.

Highlights

Mesalamine (5-aminosalicylic acid, 5-ASA), a therapeutically active moiety of Sulfasalazine1-3 is routinely employed in the treatment of inflammatory bowel disease like ulcerative colitis and Crohn’s disease
To develop the stability indicating method, first the retention behaviour of aniline compound with change in percentage of organic solvent and with change in pH of buffer was studied on Reprosil Gold100 C18-XBD column (50 mm x 2.0 mm, 1.8 μ). 1-octane sulphonic acid sodium salt ion pair reagent was used in buffer preparation to improve the peak shape and avoid the other substances co-elution at the same retention time in RP chromatography
Diluent was optimised based on solubility of aniline and mesalamine

Summary

Introduction

Mesalamine (5-aminosalicylic acid, 5-ASA), a therapeutically active moiety of Sulfasalazine is routinely employed in the treatment of inflammatory bowel disease like ulcerative colitis and Crohn’s disease. Administrated mesalamine is rapidly and almost completely absorbed from the small intestine. Mesalamine formulations which are able to deliver the intact drug to the lower intestine are nowadays successfully used. The purity evaluation of mesalamine in drug product by determination of related substances is a critical step in examination of the safety and quality of the drug product. Aniline is the critical genotoxic impurity to be considered for mesalamine drug substance and its drug product.

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