High-Performance liquid chromatographic analysis of lactone and hydroxy acid of new antitumor drug, DX-8951 (exatecan), in mouse plasma.
A sensitive high-performance liquid chromatographic (HPLC) method has been developed and validated for the determination of lactone and total drug (lactone plus hydroxy-acid) of DX-8951 in mouse plasma. Solid-phase extraction by C18 cartridge separated lactone from total drug of DX-8951. Analysis was performed using a reverse-phase ODS column with a mobile phase consisting of acetonitrile/0.05 M potassium dihydrogen phosphate (pH 3) (18: 82, v/v) at a flow rate of 1 ml/min. The limits of quantitation of lactone and total drug were 3 ng/ml in plasma and a linear range of determination were observed over the concentration of 3 to 500 ng/ml. This method was applied to pharmacokinetic study in male mice treated with a single intravenous administration of either lactone or hydroxy-acid of DX-8951. The plasma concentrations of lactone from 2 to 6 h after dosing were similar regardless of the form of DX-8951 administered.
Oguma
T
T
Drug Metabolism & Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co., Ltd.. Tokyo, Japan. ogumab0g@daiichipharm.co.jp
Yamada
M
M
Konno
T
T
Inukai
K
K
Nakaoka
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002138:Calibration; D002166:Camptothecin / Q000031:analogs & derivatives / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006880:Hydroxy Acids / Q000097:blood*; D007783:Lactones / Q000097:blood*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000970:Antineoplastic Agents; D006880:Hydroxy Acids; D007783:Lactones; C095887:exatecan; D002166:Camptothecin