title: Simultaneous determination of the peptide-mitomycin KW-2149 and its metabolites in plasma by high-performance liquid chromatography.
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-microm particle size, 150x6 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.
authors.affiliation: Laboratory of Experimental Oncology, Leuven, Belgium.
authors.forename: Z D
authors.initials: ZD
authors.lastname: Zhang
authors.forename: G
authors.initials: G
authors.lastname: Guetens
authors.forename: G
authors.initials: G
authors.lastname: De Boeck
authors.forename: K
authors.initials: K
authors.lastname: Van Cauwenberghe
authors.forename: R A
authors.initials: RA
authors.lastname: Maes
authors.forename: C
authors.initials: C
authors.lastname: Ardiet
authors.forename: A T
authors.initials: AT
authors.lastname: van Oosterom
authors.forename: M
authors.initials: M
authors.lastname: Highley
authors.forename: E A
authors.initials: EA
authors.lastname: de Bruijn
authors.forename: U R
authors.initials: UR
authors.lastname: Tjaden
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D008937:Mitomycins / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000903:Antibiotics, Antineoplastic; D008937:Mitomycins; C057625:KW 2149