High-performance liquid chromatographic method for the determination of imidazole antimycotic drugs in the presence of degraded products in oil-in-water cream

Abstract

A simple stability-indicating high performance liquid chromatographic (HPLC) method has been developed which separates imidazole antimycotic drug, clotrimazole and ketoconazole from decomposition products, other ingredients, impurities in bulk drug and cream. The suitable composition of mobile phase was found to be 2.5 mM ammonium dihydrogen phosphate pH 7.0 in methanol (3:7, v/v) with C[subscript 18] reversed-phase column as a stationary phase and UV detection at 230 nm. The proposed HPLC assay methods was used to analyze sample composed of pure antimycotic drugs and their degraded products, in comparison with BP 2002, USP 26 and NF 21. From the study obtained, the developed HPLC assay method exhibited better results than official pharmacopeial methods. In analysis of antimycotic drugs in cream, it was necessary to separate clotrimazole and ketoconazole from other ingredients in cream base before injection to HPLC instrument by using suitable sonication and freezing time. The stability of antimycotic drugs in cream was studied as a function of pH and was found to be stable at pH 4 to 8 for clotrimazole and pH 3 to 8 for ketoconazole. The HPLC method was validated and linearity was found in range 50 - 150 microgram/ml (clotrimazole) and 100-300 microgram/ml (ketoconazole) with good precision, not more than 1 % RSD for both drugs. No degradation product was found in clotrimazole and ketoconazole cream stored at 40 +- 1 ํC, 75 +- 5 % RH for six months. The proposed HPLC method might be applied satisfactorily in quantitative analysis of another drugs in imidazole group