Sensitive high-performance liquid chromatographic method for the determination of the lactone form and the lactone plus hydroxy-acid forms of the new camptothecin derivative DX-8951 in human plasma using fluorescence detection.
A sensitive quantitation of the lactone form and the lactone plus hydroxy-acid forms of DX-8951, a camptothecin derivative, in human plasma has been investigated by high-performance liquid chromatography (HPLC). This assay method consisted of two analytical procedures. In Procedure I, the lactone form was collected by the stepwise separation on a C18 cartridge. In Procedure II, the lactone plus hydroxy-acid forms were collected using another batch of the plasma sample by co-elution of the two forms from a C18 cartridge with acidic solution. The hydroxy-acid form of DX-8951 was quantitated from the difference of the lactone plus hydroxy-acid forms and the lactone form. Thereafter, these pre-treated samples were assayed by HPLC under the same HPLC conditions with a spectrofluorometer and a reverse-phase ODS column. The mobile phase was acetonitrile/0.05 M potassium dihydrogen phosphate (pH 3) (18:82, v/v) at a flow-rate of 1.0 ml/min. For the assay of the lactone form and the lactone plus hydroxy-acid forms of DX-8951 in plasma, analytical method were validated over the range 0.2-50 ng/ml.
Oguma
T
T
Drug Metabolism and Analytical Chemistry Research Laboratory, Daiichi Pharmaceutical Co. Ltd, Tokyo, Japan.
Ohshima
Y
Y
Nakaoka
M
M
D000972:Antineoplastic Agents, Phytogenic / Q000097:blood*; D002138:Calibration; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006801:Humans; D006880:Hydroxy Acids / Q000032:analysis; D007202:Indicators and Reagents; D007783:Lactones / Q000032:analysis; D012996:Solutions; D013050:Spectrometry, Fluorescence
D000972:Antineoplastic Agents, Phytogenic; D006880:Hydroxy Acids; D007202:Indicators and Reagents; D007783:Lactones; D012996:Solutions; C095887:exatecan; D002166:Camptothecin