Journal of Pharmaceutical and Biomedical Analysis 20 (1999) 99–105 Determination of miconazole in pharmaceutical creams using internal standard and second derivative spectrophotometry Kazimierz Wro ´ bel *, Katarzyna Wro ´ bel, Iliana M. de la Garza Rodrı ´guez, Pedro Luis Lo ´ pez-de-Alba, Leticia Lo ´ pez-Martı ´nez Instituto de Inestigaciones Cientı ´ficas, Uniersidad de Guanajuato, L. de Retana No. 5, 36000 Guanajuato, Mexico Received in revised form 3 December 1998; accepted 18 December 1998 Abstract A simple method is proposed for miconazole determination in pharmaceutical creams, based on extraction and second derivative spectrophotometry. In the presence of sodium lauryl sulfate (0.5%) and sulphuric acid (0.4 mol l -1 ), the miconazole and internal standard (IS) (methylene blue) were extracted to 100 l of methylene chloride. The organic phase was evaporated in the nitrogen stream and the dry residue was dissolved in methanol (1.5 ml). The analytical signal was obtained as the ratio between second derivative absorbances measured at 236.9 nm (miconazole) and at 663.2 nm (IS). The use of IS in such multi-stage procedure enabled quite good analytical performance in calibration range 50.0–400 mg l -1 : linear correlation coefficient 0.9995, precision (measured as CV for ten replicates) at 50.0 mg l -1 and at 400 mg l -1 of miconazole was 1.5 and 0.5% respectively. Four commercial pharmaceutical creams were analyzed and the results obtained were in good agreement with the results obtained by reversed-phase high performance liquid chromatography (HPLC). © 1999 Elsevier Science B.V. All rights reserved. Keywords: Miconazole; Internal standard; Derivative spectrophotometry; Pharmaceutical creams 1. Introduction Miconazole is a drug of wide antifungal spec- trum. It is administered by the troche dosage form or by the intravenous infusion in the treatment of severe systemic fungal infections, or applied as a 2% cream or powder in infections of nails and skin [1]. Several analytical procedures have been pro- posed for the quantification of miconazole in pharmaceuticals [2–5] and in biological fluids [6– 9]. For clinical samples, high performance liquid chromatography (HPLC) was used. Before intro- duction on the ODS column, the samples were deproteinized with acetonitrile [8]. Separation of miconazole was also achieved by liquid – liquid extraction [7] and solid phase extraction [6]. Szathmary et al. determined miconazole in human plasma using a multi-stage separation/preconcen- * Corresponding author. Fax: +52-473-26252. E-mail address: katarzyn@quijote.ugto.mx (K. Wro ´ bel) 0731-7085/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved. PII:S0731-7085(98)00313-6