P. De Bruijn et al., Liquid chromatographic determination of ketoconazole, a potent inhibitor of CYP3A4-mediated metabolism, J CHROMAT B, 753(2), 2001, pp. 395-400
A high-performance liquid chromatographic assay with UV detection has been
developed for the determination of ketoconazole in human plasma. Quantitati
ve extraction was achieved by a single solvent extraction involving a mixtu
re of acetonitrile-n-butyl chloride (1:4, v/v). Ketoconazole and the intern
al standard (clotrimazole) were separated on a column packed with Inertsil
ODS-80A material and a mobile phase composed of wa( er-acetonitrile-tetrahy
drofuran-ammonium hydroxide-triethylamine (45:50.2:2.5:0.1:0.1, v/v). The c
olumn effluent was monitored at a wavelength of 206 nm with a detector rang
e set at 0.5. The calibration graph was linear in the range of 20-2000 ng/m
l, with a lower limit of quantitation of 20.0 ng/ml. The extraction recover
ies for ketoconazole and clotrimazole in human plasma were 93 +/- 9.7% and
83 +/- 10.0%, respectively. The developed method has been successfully appl
ied to a clinical study to examine the pharmacokinetics of ketoconazole in
a cancer patient. (C) 2001 Elsevier Science B.V. All rights reserved.