Abstract
Sulfasalazine (SSZ) was subjected to degradation under the conditions of hydrolysis (acid, alkali, and water), oxidation (30% H2O2), dry heat, and photolysis (UV-VIS light) in accordance with the ICH guidelines. An RP-HPLC method was developed to study the degradation behavior. No degradation was noted under any condition except alkaline hydrolysis where SSZ was degraded to a single minor product. SSZ was optimally resolved from this product on an XTerra® RP18 column with a mobile phase composed of methanol and an ammonium acetate buffer (10 mM, pH 7.0) (48:52, v/v) delivered at a rate of 0.8 mL/min in an isocratic mode. The method was validated and found to be linear (r2=0.99945), precise (%RSD <2), robust, and accurate (94–102%) in the concentration range of 0.5–50 μg/mL of SSZ. The PDA analysis of the degraded sample revealed the SSZ peak purity to be 998.99 and the drug peak eluted with a resolution factor of >2 from the nearest resolving peak, indicating the method to be selectively stability-indicating for the drug analysis. The method was applied successfully for the stability testing of the commercially available SSZ tablets that were under varied ICH-prescribed conditions. An explanation for the unusual stability of the drug when exposed to acidic hydrolysis, despite the presence of the sulfonamide linkage, is also discussed.
Highlights
Sulfasalazine (SSZ), 2-Hydroxy-5-[(E)-2-{4-[(pyridin-2-yl)sulfamoyl]phenyl}diazen-1-yl]benzoic acid (Fig. 1), is a disease-modifying, anti-rheumatic drug which helps to reduce joint pain, swelling, and stiffness [1]
The International Conference on Harmonization (ICH), through its guidelines Q1A (R2) and Q1B [10, 11], requires the conduct of forced degradation studies to characterize all of the possible degradation products under varied conditions such as light, heat, humidity, acid/base hydrolysis, and oxidation in order to develop a stability-indicating assay method (SIAM) for the stability testing of a drug substance or product
The present study was undertaken to carry out the ICH-prescribed forced degradation study on SSZ to characterize the degradation products and to develop and validate a stability-indicating HPLC method
Summary
Sulfasalazine (SSZ), 2-Hydroxy-5-[(E)-2-{4-[(pyridin-2-yl)sulfamoyl]phenyl}diazen-1-yl]benzoic acid (Fig. 1), is a disease-modifying, anti-rheumatic drug which helps to reduce joint pain, swelling, and stiffness [1]. While the sulfonamide linkage is susceptible to hydrolysis in acidic medium [4] to form the corresponding sulfonic acid derivative and amine, the azo group can undergo chemical changes under hydrolytic, photolytic, and oxidative conditions to form different products [5,6,7,8] The photolytic studies were carried out by exposing a thin layer of the solid drug in a Petri dish, as well as solutions of the drug in 1 N HCl, water, and 1 N NaOH to the light in the photostability chamber for 10 days, during which the total fluorescent light exposure was equaled to 1.2 million lux h and UV exposure was 200 watt hm−2. The alkali and acid samples were neutralized with acid or alkali, before dilution
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