Use of a validated stability-indicating HPTLC method to study the degradation of rimonabant

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Abstract

Rimonabant (RIM) is a synthetic cannabinoid CB 1 receptor antagonist being developed for the treatment of multiple cardiometabolic risk factors, including abdominal obesity and smoking. This paper describes development and subsequent validation, in accordance with International Conference on Harmonization (ICH) guidelines, of a simple, sensitive, selective, precise, and stability-indicating HPTLC method for analysis of rimonabant. Silica gel plates were used with methanol-water 7:3 ( v/v ) as mobile phase. Densitometry was performed at 250 nm. Compact bands were obtained at RF 0.71 ± 0.02. Linear regression analysis of calibration data revealed good linear relationship with r2 = 0.9985 in the working concentration range of 100–800 ng per band. The method was validated for precision, accuracy, ruggedness, robustness, specificity and recovery. The drug was subjected to acidic and alkaline hydrolysis, oxidation, dry heat, UV irradiation, and photodegradation in daylight. The peaks of degradation products were well resolved from that of the drug with significantly different RF values. Statistical analysis showed the method is reproducible and selective. Because the method effectively separates the drug from its degradation products, it can be regarded as stability-indicating. The method enabled successful analysis of marketed formulations of rimonabant and was also used to investigate the kinetics of acidic and alkaline degradation at different temperatures. An Arrhenius plot was constructed and apparent pseudo-first-order rate constant, half-life, and activation energy were calculated. The pH-rate profile for degradation of rimonabant in constant-ionic-strength buffer solutions was studied in the pH range 1.2–10.8.

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