Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.jchromb.2005.05.010
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dc.titleSimultaneous determination of the lactone and carboxylate forms of irinotecan (CPT-11) and its active metabolite SN-38 by high-performance liquid chromatography: Application to plasma pharmacokinetic studies in the rat
dc.contributor.authorYang, X.
dc.contributor.authorHu, Z.
dc.contributor.authorSui, Y.C.
dc.contributor.authorChan, E.
dc.contributor.authorZhou, S.
dc.contributor.authorGoh, B.C.
dc.contributor.authorDuan, W.
dc.date.accessioned2011-09-29T06:43:09Z
dc.date.available2011-09-29T06:43:09Z
dc.date.issued2005
dc.identifier.citationYang, X., Hu, Z., Sui, Y.C., Chan, E., Zhou, S., Goh, B.C., Duan, W. (2005). Simultaneous determination of the lactone and carboxylate forms of irinotecan (CPT-11) and its active metabolite SN-38 by high-performance liquid chromatography: Application to plasma pharmacokinetic studies in the rat. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 821 (2) : 221-228. ScholarBank@NUS Repository. https://doi.org/10.1016/j.jchromb.2005.05.010
dc.identifier.issn15700232
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/27429
dc.description.abstractIrinotecan (CPT-11) and its main metabolite SN-38 are potent anticancer derivatives of camptothecin (CPT), with active lactone and inactive carboxylate forms coexisting. A simple and sensitive HPLC method using the ion-pairing reagent tetrabutylammonium hydrogen sulfate (TBAHS) was developed to simultaneously determine all four analytes in rat plasma samples. Camptothecin (CPT) was used as internal standard. The mobile phase was 0.1 M potassium dihydrogen phosphate containing 0.01 M TBAHS (pH 6.4)-acetonitrile (75:25, v/v). Separation of the compounds was carried out on a Hypersil C18 column, monitored at 540 nm (excitation wavelength at 380 nm). All four compounds gave linear response as a function of concentration over 0.01-10 μM. The limit of quantitation in rat plasma was 0.01, 0.008, 0.005 and 0.005 μM for CPT-11 lactone, CPT-11 carboxylate, SN-38 lactone and SN-38 carboxylate, respectively. The method was successfully used in the study on the effect of coadministered thalidomide on the plasma pharmacokinetics of CPT-11 and SN-38 in rats. Coadministered thalidomide (100 mg/kg body weight by intraperitoneal injection) significantly increased the AUC0-10h values of CPT-11 lactone and CPT-11 carboxylate by 32.6% and 30.3 %, respectively, (P < 0.01), but decreased the values by 19.2% and 32.4% for SN-38 lactone and carboxylate, respectively, (P < 0.05). Accordingly, the value of total body clearance (CL) of CPT-11 lactone was significantly lower in combination group compared to the control (1.329 versus 1.837 L/h/kg, P = 0.0002). Plasma t1/2β values for SN-38 lactone and carboxylate were significantly (P < 0.01) smaller in rats with coadministered thalidomide, as compared to rats receiving CPT-11 alone. Further studies are needed to explore the underlying mechanisms for the observed kinetic interaction between CPT-11 and thalidomide. © 2005 Elsevier B.V. All rights reserved.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/j.jchromb.2005.05.010
dc.sourceScopus
dc.subjectCarboxylate
dc.subjectHPLC
dc.subjectIrinotecan
dc.subjectLactone
dc.subjectSN-38
dc.typeArticle
dc.contributor.departmentBIOCHEMISTRY
dc.contributor.departmentPHARMACOLOGY
dc.contributor.departmentPHARMACY
dc.description.doi10.1016/j.jchromb.2005.05.010
dc.description.sourcetitleJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
dc.description.volume821
dc.description.issue2
dc.description.page221-228
dc.identifier.isiut000230214500015
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