title: Determination of the stereoisomers in aqueous medium and serum and validation studies of racemic aminoalkanol derivatives of 1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.0(2,6) ]dec-8-ene-3,5,10-trione, potential new anticancer drugs, by capillary electrophoresis.
abstract: A new method for the determination of the stereoisomers, in aqueous medium and serum, of the racemic aminoalkanol derivatives I and II of 1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.0(2,6) ]dec-8-ene-3,5,10-trione, which were found in earlier studies to be potential anticancer drugs, was developed and validated. The optimized conditions included 25 mM phosphate buffer adjusted to pH 2.5, containing γ-cyclodextrin at a concentration of 5% m/v, as background electrolyte, an applied voltage of +10 kV, and a temperature of 25°C. Separations were carried out using a fused-silica capillary. The developed method of determining the enantiomers of compounds I(S), I(R) and II(S), II(R) was characterized by the following parameters: a detection time within 10.8 min, a detection limit in the range of 141.2-141.7 ng/mL using the UV absorption detection at 200 nm. Good linearity (R(2) = 0.9989-0.9998) was achieved within the range of concentrations studied. A very good extraction yield of 95.4-99.7% was achieved, and recoveries were carried out from both aqueous solutions and matrix serum. The repeatability of the method for peak areas with an accuracy of the determined concentrations of the analytes in the range of 1.43-1.89%, and limits of quantitation in the range of 432.4-436.3 ng/mL were achieved.
authors.affiliation: Chair and Department of Biochemistry and Clinical Chemistry, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Błażej
authors.initials: B
authors.lastname: Grodner
authors.affiliation: Chair and Department of Biochemistry and Clinical Chemistry, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Łukaszkiewicz
authors.affiliation: Chair and Department of Biochemistry, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Mariola
authors.initials: M
authors.lastname: Napiórkowska
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D006575:Heterocyclic Compounds, 3-Ring / Q000097:blood / Q000737:chemistry*; D006801:Humans; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D006575:Heterocyclic Compounds, 3-Ring
keywords: Anticancer drugs; Capillary electrophoresis; Drug monitoring