Simultaneous determination of the lactone and carboxylate forms of irintecan (CPT-11) and its actie metabolite SN-38 by high-performance liquid chromatography: Application to plasma pharmacokinetic studies in the rat.

Yang, Xiaoxia, Hu, Zeping, Chan, Sui Yung, Goh, Boon Cher, Duan, Wei, Chan, Eli and Zhou, Shufeng 2005, Simultaneous determination of the lactone and carboxylate forms of irintecan (CPT-11) and its actie 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, vol. 821, no. 2, pp. 221-228.

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Title Simultaneous determination of the lactone and carboxylate forms of irintecan (CPT-11) and its actie metabolite SN-38 by high-performance liquid chromatography: Application to plasma pharmacokinetic studies in the rat.
Author(s) Yang, Xiaoxia
Hu, Zeping
Chan, Sui Yung
Goh, Boon Cher
Duan, Wei
Chan, Eli
Zhou, Shufeng
Journal name Journal of chromatography. B, analytical technologies in the biomedical and life sciences
Volume number 821
Issue number 2
Start page 221
End page 228
Publisher Elsevier B.V.
Place of publication Amsterdam, The Netherlands
Publication date 2005-07-25
ISSN 1570-0232
1873-376X
Keyword(s) HPLC
irinotecan
SN-38
lactone
carboxylate
Summary 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.
Language eng
Field of Research 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2005, Elsevier B.V.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30009159

Document type: Journal Article
Collection: School of Medicine
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