title: High-performance liquid chromatographic analysis of the new antitumour drug SK&F 104864-A (NSC 609699) in plasma.
abstract: A high-performance liquid chromatographic (HPLC) assay is described for the determination of the new, investigational antitumour drug SK&F 104864-A and its lactone ring opened form (SK&F 105992). The analytical methodology reported here involves a protein precipitation step with methanol as sample pretreatment procedure. The instability of the drug necessitates that the plasma fraction is obtained within 5 min after blood sampling by centrifugation, immediately followed by protein precipitation with cold methanol (-30 degrees C). The methanolic extract can be stored at -30 degrees C for several days without deterioration of the analyses. Stability data of the drug and its lactone ring opened metabolite in plasma and after methanolic extraction are discussed. The parent drug and the metabolite are separated by reversed-phase ion-pair liquid chromatography on a LiChrosorb RP-18 column, using methanol-water eluent (pH 6.0) with sodium dioctylsulphosuccinate (DOSS) as ion-pairing agent and fluorescence detection. The proposed method has been validated and, subsequently, implemented in a phase I clinical trial for pharmacokinetic evaluation of the new cytotoxic agent.
authors.affiliation: Slotervaart Hospital, Amsterdam, The Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: B R
authors.initials: BR
authors.lastname: Smith
authors.forename: W J
authors.initials: WJ
authors.lastname: Keijer
authors.forename: R
authors.initials: R
authors.lastname: van Gijn
authors.forename: W W
authors.initials: WW
authors.lastname: ten Bokkel Huinink
authors.forename: L T
authors.initials: LT
authors.lastname: Vlasveld
authors.forename: S
authors.initials: S
authors.lastname: Rodenhuis
authors.forename: W J
authors.initials: WJ
authors.lastname: Underberg
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004355:Drug Stability; D006801:Humans; D013050:Spectrometry, Fluorescence; D019772:Topotecan
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan; D002166:Camptothecin