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.title | 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 | |
dc.contributor.author | Yang, X. | |
dc.contributor.author | Hu, Z. | |
dc.contributor.author | Sui, Y.C. | |
dc.contributor.author | Chan, E. | |
dc.contributor.author | Zhou, S. | |
dc.contributor.author | Goh, B.C. | |
dc.contributor.author | Duan, W. | |
dc.date.accessioned | 2011-09-29T06:43:09Z | |
dc.date.available | 2011-09-29T06:43:09Z | |
dc.date.issued | 2005 | |
dc.identifier.citation | Yang, 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.issn | 15700232 | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/27429 | |
dc.description.abstract | Irinotecan (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.uri | http://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/j.jchromb.2005.05.010 | |
dc.source | Scopus | |
dc.subject | Carboxylate | |
dc.subject | HPLC | |
dc.subject | Irinotecan | |
dc.subject | Lactone | |
dc.subject | SN-38 | |
dc.type | Article | |
dc.contributor.department | BIOCHEMISTRY | |
dc.contributor.department | PHARMACOLOGY | |
dc.contributor.department | PHARMACY | |
dc.description.doi | 10.1016/j.jchromb.2005.05.010 | |
dc.description.sourcetitle | Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | |
dc.description.volume | 821 | |
dc.description.issue | 2 | |
dc.description.page | 221-228 | |
dc.identifier.isiut | 000230214500015 | |
Appears in Collections: | Staff Publications |
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