Supercritical Fluid Extraction of Imidazole Drugs from Cosmetic and Pharmaceutical Products

WEI-LUNG CHOU¹, CHING-YAO CHANG², HUI-MING LIU¹*, KAI-CHIANG YANG¹ AND CHIA-CHAN WU¹

1. Department of Industrial Safety and Health, Hung Kuang University, Shalu, Taichung 433, Taiwan, R.O.C.
^2. Department of Biotechnology and Bioinformatics, Asia University, Wufeng, Taichung 413, Taiwan, R.O.C.

(Received: July 12, 2006; Accepted: September 13, 2006)

Abstract

   An effective method for isolating common imidazole drugs clotrimazole (CT) and ketoconazole (KCZ) from cosmetic and pharmaceutical products based on supercritical fluid extraction (SFE) was developed.  Creams, tablets and cosmetic shampoos underwent supercritical carbon dioxide fluid extraction and CT and KCZ were determined by reverse-phase high performance liquid chromatography.  All supercritical fluid extractions were performed with a 10-min static step, followed by a 15 min dynamic step using acetonitrile as the modifier.  After extraction by SFE, KCZ and CT were separated on a C₁₈ column using an isocratic mobile phase that consisted of methanol/water/diethylamine/glacial acetic acid (80:20:0.3:0.2, v/v, pH 7.0) at a flow rate of 1.0 mL/min.  The eluates from column were monitored by absorbance at 224 nm using a diode array detector.

   This developed approach was validated by assaying commercial pharmaceuticals for the routine quantification of CT and KCZ in various formulations.  The calibration curves for CT and KCZ were linear over the ranges of 50~250 μg/mL and 25~250 μg/mL, respectively.  The detection limits of CT and KCZ were 2.31 μg/mL and 0.42 μg/mL, respectively, and the limits of quantitation were 7.70 μg/mL and 1.40 μg/mL, respectively.  These drugs contents were found to be in good agreement with the label claim values.  Satisfactory extraction recoveries ranging from 90.8% to 97.2% were obtained from five replicate extractions.

Key words: supercritical fluid extraction, clotrimazole (CT), ketoconazole (KCZ), imidazole drugs