Liquid chromatographic determination of ketoconazole, a potent inhibitor of CYP3A4-mediated metabolism |
| |
| Authors: | Peter de Bruijn Diederik F S Kehrer Jaap Verweij Alex Sparreboom |
| |
| Institution: | 1. Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Av. Ipiranga 6681 – Prédio 92A Tecnopuc, 90619-900 Porto Alegre, RS, Brazil;2. Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga 6681 – Prédio 92A Tecnopuc, 90619-900 Porto Alegre, RS, Brazil;3. Programa de Pós-Graduação em Biologia Celular e Molecular, PUCRS, Porto Alegre, Brazil;4. Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil;5. Programa de Pós-Graduação em Medicina e Ciências da Saúde, PUCRS, Porto Alegre, Brazil;6. Instituto de Toxicologia e Farmacologia, PUCRS, Porto Alegre, Brazil |
| |
| Abstract: | A high-performance liquid chromatographic assay with UV detection has been developed for the determination of ketoconazole in human plasma. Quantitative extraction was achieved by a single solvent extraction involving a mixture of acetonitrile–n-butyl chloride (1:4, v/v). Ketoconazole and the internal standard (clotrimazole) were separated on a column packed with Inertsil ODS-80A material and a mobile phase composed of water–acetonitrile–tetrahydrofuran–ammonium hydroxide–triethylamine (45:50.2:2.5:0.1:0.1, v/v). The column effluent was monitored at a wavelength of 206 nm with a detector range set at 0.5. The calibration graph was linear in the range of 20–2000 ng/ml, with a lower limit of quantitation of 20.0 ng/ml. The extraction recoveries for ketoconazole and clotrimazole in human plasma were 93±9.7% and 83±10.0%, respectively. The developed method has been successfully applied to a clinical study to examine the pharmacokinetics of ketoconazole in a cancer patient. |
| |
| Keywords: | Ketoconazole |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
