Stability Indicating Methods for the Determination of some Anti-fungal Agents Using Densitometric and RP-HPLC Methods

抄録

Two chromatographic methods were developed for the determination of some anti-fungal drugs in the presence of either their degradation products or cortisone derivatives. The densitometric method determined mixtures of each of ketoconazole (KT), clotrimazole (CL), miconazole nitrate (MN) and econazole nitrate (EN) with the degradation products of each one. Mixtures of MN with hydrocortisone (HC) and of EN with triamcinolone acetonide (TA) were also successfully separated and determined by this technique. For KT and CL, a mixture of methanol : water : triethylamine (70 : 28 : 2 v/v) was used as a developing system and the spots were scanned at 243 nm and 220 nm for KT and CL, respectively. For MN and EN, a mixture of hexane : isopropyl alcohol : triethylamine (80 : 17 : 3 v/v) was used as a developing system and the spots were scanned at 225 nm for both drugs. The HPLC method determined mixtures of CL or EN with their degradation products which were separated and quantified on a Zorbax C8 column. Elution was carried out using methanol : phosphate buffer pH 2.5 (65 : 35 v/v) as a mobile phase at a flow rate of 1.5 ml/min and UV detection at 220 nm for CL. For EN, a mixture of methanol : water containing 0.06 ml triethylamine pH 10 (75 : 25 v/v) was used as a mobile phase at a flow rate of 1.5 ml/min and UV detection at 225 nm. The methods were also used to separate mixtures of CL with betamethasone dipropionate (BD) and EN with TA in a laboratory prepared mixture and in pharmaceutical preparations. The methods were sensitive, precise and applicable for determination of the drugs in pharmaceutical dosage forms.