Monitoring of trace amounts of some anti-fungal drugs in biological fluids by hollow fiber based liquid phase microextraction followed by high performance liquid chromatography

This paper reports the applicability of hollow fiber based liquid phase microextraction (HF-LPME) for the extraction of three anti-fungal drugs (Ketoconazole (KZ), Clotrimazole (CZ) and Miconazole (MZ)) from biological fluids. The drugs were extracted from 10 mL of the aqueous sample into an organic phase with microliter volume located inside the pores of a polypropylene hollow fiber, and then back extracted into 24 mu L of a second aqueous solution (pH 2.5) located inside the lumen of the hollow fiber. The effects of organic solvent, stirring rate, salt concentration, pH of the source and receiving phases and extraction time on the extraction recovery were investigated and optimized. Under optimized conditions preconcentration factors for KZ, CZ and MZ were obtained as 133, 127.9 and 71, respectively. The calibration curves were linear (r(2) >= 0.99) in the concentration range of 5.0-500 mu g L-1 for both KZ and CZ and 8.0-500 mu g L-1 for MZ. The limits of detections (LODs) for KZ, CZ and MZ were obtained as 0.9 mu g L-1, 1.8 mu g L-1 and 4.0 mu g L-1, respectively. The intra-day and inter-day RSD% based on 5 replicates were obtained as <= 6.3% and <= 12.1%, respectively. The method was successfully applied for determining the concentration of the drugs in plasma and urine samples.