Simultaneous determination of the peptide-mitomycin KW-2149 and its metabolites in plasma by high-performance liquid chromatography |
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| Authors: | Z. D. Zhang G. Guetens G. De Boeck K. Van Cauwenberghe R. A. A. Maes C. Ardiet A. T. van Oosterom M. Highley E. A. de Bruijn U. R. Tjaden |
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| Affiliation: | a Laboratory of Experimental Oncology, Herestraat 49, B-3000 Leuven, Belgium;b Department of Chemistry, University of Antwerp, Antwerp, 2610-Wilrijk, Belgium;c Netherlands Institute of Drug and Doping Research, University of Utrecht, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands;d Centre Regional Leon Berard 28, Rue Laënnec 69373, Lyon Cedex 08, France;e PTLF, PO Box 192, NL-4500 Oostburg, The Netherlands;f Divison of Biopharmaceutical Sciences, University of Leiden, NL 2300 RA Leiden, The Netherlands |
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| Abstract: | A gradient high-performance liquid chromatographic (HPLC) method is described for the quantification of KW-2149 and its two major metabolites in plasma. The method involves a sample clean-up by solid-phase extraction on C18 columns, separation of the respective compounds by HPLC on a YMC ODS-AQ column (5-μm particle size, 150×6 mm I.D.), using a methanol–water gradient system as an eluent, and measurement by UV absorbance detection at 375 nm. The limits of quantitation were 10 ng/ml for KW-2149 and M-16, and 15 ng/ml for M-18. Recoveries from plasma were higher than 92% on C18 extraction columns. Intra-day precision, expressed as %C.V., was between 1.4 and 6.5%. Intra-day accuracy ranged from 94 to 107%. Precision and accuracy of variability of inter-assays increased somewhat; however, were still within acceptable ranges. The ability of the method to quantify KW-2149 and two major metabolites simultaneously, with precision, accuracy and sensitivity, make it useful in monitoring the fate of this new mitomycin in cancer patients. |
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| Keywords: | Peptide-mitomycin KW-2149 |
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