Simple and rapid determination of irinotecan and its metabolite SN-38 in plasma by high-performance liquid-chromatography:: application to clinical pharmacokinetic studies

被引:55
作者
Escoriaza, J
Aldaz, A
Castellanos, C
Calvo, E
Giráldez, J
机构
[1] Univ Navarra Clin, Serv Farm, Pamplona 31008, Spain
[2] Univ Navarra Clin, Dept Oncol, Pamplona 31008, Spain
来源
JOURNAL OF CHROMATOGRAPHY B | 2000年 / 740卷 / 02期
关键词
HPLC; pharmacokinetics; irinotecan; SN-38;
D O I
10.1016/S0378-4347(00)00048-7
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Irinotecan (CPT-11) is an anticancer agent widely employed in the treatment of colorectal carcinoma. A simple, rapid and sensitive high-performance liquid chromatographic method for the simultaneous determination of CPT-11 and its metabolite SN-38 in plasma, and their preliminary clinical pharmacokinetics are described. Both deproteinisation of plasma specimens (100 mu l) and addition of the internal standard, camptothecin (CPT), are achieved by incorporating to samples 100 mu l of a solution of CPT (1 mu g/ml) in acetonitrile-1 mM orthophosphoric acid (90:10); 200 mu l of this acidified acetonitrile solution, drug-free, is also added to accomplish complete deproteinisation: this procedure reduces sample preparation time to a minimum. After deproteinisation, samples are treated with potassium dihydrogenphosphate (0.1 M) and injected into a Nucleosil C-18 (5 mu m, 250x4.0 mm) column. Mobile phase consists of potassium dihydrogenphosphate (0.1 M)-acetonitrile (67:33),at a flow-rate of 1 ml/min. CPT-11, SN-38 and CPT are detected by fluorescence with excitation wavelength set at 228 nm and emission wavelengths of CPT-11, SN-38: and CPT fixed, respectively, at 450, 543 and 433 nm. The limits of quantitation for CPT-11 and SN-38 are 1.0 and 0.5 ng/ml, respectively. This method shows good precision: the within day relative standard deviation (RSD) for CPT-11 (1-10 000 ng/ml) is 5.17% (range 2.15-8.27%) and for SN-38 (0.5-400 ng/ml) is 4.33% (1.32-7.78%); the between-day RSDs for CPT-11 and SN-38, in the previously described ranges, are 6.82% (5.03-10.8%) and 4.94% (2.09-9.30%), respectively. Using this assay, plasma pharmacokinetics of CPT-11, SN-38 and its glucuronidated form, SN-38G, have been determined in one patient receiving 200 mg/m(2) of CPT-11 as a 90 min intravenous infusion. The peak plasma concentration of CPT-11 at the end of the infusion is 3800 ng/ml. Plasma decay is biphasic with a terminal half-life of 11.6 h. The volume of distribution at steady state (V-ss) is 203 1/m(2), and the total body clearance (Cl) is 14.8 1/h.m(2). The maximum concentrations of SN-38 and SN-38G reach 28.9 and 151 ng/ml, respectively. (C) 2000 Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:159 / 168
页数:10
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