Journal
THERAPEUTIC DRUG MONITORING
Volume 25, Issue 1, Pages 120-124Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00007691-200302000-00020
Keywords
irinotecan; CPT-11; SN-38; bioanalysis; high-performance liquid chromatography (HPLC)
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A rapid, sensitive, and specific high-performance liquid chromatography (HPLC) method for the simultaneous determination of irinotecan (CPT-11) and its active metabolite SN-38 in human plasma is described. The analytes are quantified as the totals of their carboxylate and lactone form. The sample pretreatment consisted of a simple protein precipitation with acetonitrile-methanol (1:1, v/v), after which CPT-11 and SN-38 were quantitatively converted to their carboxylate form by adding 0.01 mol/L sodium tetraborate (pH, 9). Chromatography was carried out on a Zorbax SB-C18 column with fluorescence detection. The method has been validated, and stability tests under various clinically relevant conditions have been performed. The lower limit of quantification (LLOQ) was 5.0 ng/mL for CPT-11 and 0.5 ng/mL for SN-38. Standard concentration ranges were linear between 5 and 1,500 ng/mL for CPT-11 and between 0.5 and 100 ng/mL for SN-38. This assay is simple, rapid, and very useful for therapeutic monitoring of CPT-11 and SN-38.
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