期刊
TALANTA
卷 76, 期 5, 页码 1015-1021出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.talanta.2008.04.058
关键词
irinotecan (CPT-11); SN-38; plasma; bile; ultraviolet detection; pharmacokinetics
资金
- Council of Scientific & Industrial Research (CSIR), New Delhi, India
A new, simple. sensitive and specific reversed-phase high performance liquid chromatographic (HPLC) method using ultraviolet detection was developed and validated for the analysis of CPT-11 (lambda(max) = 254 nm, 365 nm) and its major active metabolite, SN-38 (lambda(max) = 380 nm) in rat plasma and bile. The sample pretreatment from plasma involved a single protein precipitation step with cold acetonitrile. In case of bile, liquid-liquid extraction with dichloromethane: tert-butyl methyl ether (3:7) was carried out. Topotecan, a structurally related camptothecin, was used as an internal standard. An aliquot of 50 mu L was injected onto a C-18 column. The chromatographic separation was achieved by gradient elution consisting of acetonitrile and water (pH 3.0 adjusted with 20% o-phosphoric acid) at a flow rate of 1.0 ml/min. Total run time for each sample was 30 min. All the analytes viz. topotecan. CPT-11, SN-38 were well separated with retention times of 11.4. 13.4 and 15.5 min, respectively. Method was found to be selective, linear (R-2 approximate to 0.999), accurate (recovery +/- 15%) and precise (<5% C.V.) in the selected concentration ranges for both the analytes. The quantification limit for CPT-11 was 40 ng ml(-1) and for SN-38 was 25 ng ml(-1). The percent extraction efficiency was similar to 97% for CPT-11 and SN-38 from plasma while extraction recovery of CPT-11 and SN-38 from bile was similar to 70% and similar to 60%, respectively. The method was successfully used to determine plasma and biliary excretion time profiles of CPT-11 and SN-38, following oral and intravenous CPT-11 administration in rats. In the present study, irinotecan showed an absolute bioavailability of 30% as calculated from the pharmacokinetic data. (C) 2008 Elsevier B.V. All rights reserved.
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