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Titolo:
Simultaneous determination of etoposide and its catechol metabolite in theplasma of pediatric patients by liquid chromatography/tandem mass spectrometry
Autore:
Pang, SK; Zheng, NY; Felix, CA; Scavuzzo, J; Boston, R; Blair, IA;
Indirizzi:
Univ Penn, Dept Pharmacol, Ctr Canc Pharmacol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Pharmacol, Philadelphia, PA 19104 USA Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Oncol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Div Oncol, Philadelphia, PA 19104 USA Univ Penn, Sch Vet Med, Biomath Unit, Kennett Sq, PA 19348 USA Univ Penn Kennett Sq PA USA 19348 Biomath Unit, Kennett Sq, PA 19348 USA
Titolo Testata:
JOURNAL OF MASS SPECTROMETRY
fascicolo: 7, volume: 36, anno: 2001,
pagine: 771 - 781
SICI:
1076-5174(200107)36:7<771:SDOEAI>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
STRANDED PHI-X174 DNA; ELECTROCHEMICAL DETECTION; TOPOISOMERASE-II; FLUORESCENCE DETECTION; CYTOCHROME-P450 3A4; O-DEMETHYLATION; ORTHO-QUINONE; VP 16-213; VP-16-213; CANCER;
Keywords:
etoposide; catechol metabolite; plasma; high-performance liquid chromatography; tandem mass spectrometry;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Physical, Chemical & Earth Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Blair, IA Univ Penn, Dept Pharmacol, Ctr Canc Pharmacol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Philadelphia, PA 19104 USA
Citazione:
S.K. Pang et al., "Simultaneous determination of etoposide and its catechol metabolite in theplasma of pediatric patients by liquid chromatography/tandem mass spectrometry", J MASS SPEC, 36(7), 2001, pp. 771-781

Abstract

The anticancer drug etoposide is associated with leukemias with MLL gene translocations and other translocations as a treatment complication. The genotype of cytochrome P450 3A4 (CYP3A4), which converts etoposide to its catechol metabolite, influences the risk. In order to perform pharmacokinetic studies aimed at further elucidation of the translocation mechanism, we havedeveloped and validated a liquid chromatography/electrospray/tandem mass spectrometry assay for the simultaneous analysis of etoposide and its catechol metabolite in human plasma. The etoposide analog teniposide was used as the internal standard. Liquid chromatography was performed on a YMC ODS-AQ column. Simultaneous determination of etoposide and its catechol metabolitewas achieved using a small volume of plasma, so that the method is suitable for pediatric patients. The limits of detection were 200 ng ml(-1) etoposide and 10 ng ml(-1) catechol metabolite in human plasma and 25 ng ml(-1) etoposide and 2.5 ng ml-1 catechol metabolite in protein-free plasma, respectively. Acceptable precision and accuracy were obtained for concentrations in the calibration curve ranges 0.2-100 mug ml(-1) etoposide and 10-5000 ngml(-1) catechol metabolite in human plasma. Acceptable precision and accuracy for protein-free human plasma in the range 25-15000 ng ml(-1) etoposideand 2.5-1500 ng ml(-1) etoposide catechol were also achieved. This method was selective and sensitive enough for the simultaneous quantitation of etoposide and its catechol as a total and protein-free fraction in small plasma volumes from pediatric cancer patients receiving etoposide chemotherapy. A pharmacokinetic model has been developed for future studies in large populations. Copyright (C) 2001 John Wiley & Sons, Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 12:29:03