Challenges in Simultaneous Analysis of Hydrolytically Sensitive Ester drugs in Combined Dosage Forms

Abstract:

Objective: Two or more ester drugs in multicomponent formulations are likely to exhibit errors during analysis under acidic conditions, possibly due to hydrolysis. UV Spectrometric methods are hard to disseminate such phenomenon while HPLC methods could provide an insight into possible degradations as source for erroneous conclusions. Material and Methods: Combined dosage formulation of aspirin and clopidogrel bisulphate has been used in the study to demonstrate limitations of popular Absorbance Ratio method commonly used for simultaneous determination by UV spectroscopy. Results: Under acidic hydrolytic conditions, clopidogrel degradation was found to increase in presence of aspirin as shown by HPLC method. Validated HPLC method used for the study comprised of mobile phase methanol: 10 mM phosphate buffer (80:20), pH 7 and a C-18 Column. Rt for aspirin and clopidogrel bisulphate were found to be 2.1 and 7.3 min respectively, with flow rate of 1 mL/min. For absorbance ratio method mixture of methanol: 0.1 N HCl was used as the solvent. Conclusion: In the event of unexpected challenges involving stability of drugs in solutions, it becomes necessary to search for platforms that prevents degradation and subsequently prevent possible interactions between degradants if any.

Key words: Absorbance Ratio, HPLC, Aspirin, Clopidogrel, Hydrolysis, Degradation.