High-performance liquid chromatographic analysis of the antitumour drug camptothecin and its lactone ring-opened form in rat plasma.
A sensitive high-performance liquid chromatographic (HPLC) method is described for the simultaneous determination of the antitumour drug camptothecin (I) and its lactone ring-opened form (II) in plasma. The sample pretreatment involved protein precipitation with cold methanol (-30 degrees C). The methanolic extract was injected directly onto the HPLC column. Chromatography was carried out with a LiChrosorb RP-18 column (particle size 5 microns) and a mobile phase composed of methanol-phosphate buffer (5 mM, pH 6.5)-0.3 M tetrabutylammonium phosphate solution (500:500:15, v/v/v). The column effluent was monitored spectrofluorimetrically with the excitation wavelength set at 369 nm and the emission wavelength at 426 nm. The chemical stabilities of camptothecin and the ring-opened form in aqueous solutions, in plasma and after methanolic extraction, were investigated. The proposed method was validated and utilized in pharmacokinetic studies with rats.
Slotervaart Hospital, Amsterdam, Netherlands.
J H
JH
Beijnen
H
H
Rosing
W W
WW
ten Bokkel Huinink
H M
HM
Pinedo
D000818:Animals; D002166:Camptothecin / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D007783:Lactones / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence
D007783:Lactones; D002166:Camptothecin