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Titolo:
Validated high-performance liquid chromatographic assay for simultaneous determination of dacarbazine and the plasma metabolites 5-(3-hydroxymethyl-3-methyl-1-triazeno)imidazole-4-carboxamide and 5-(3-methyl-1-triazeno)imidazole-4-carboxamide
Autore:
Safgren, SL; Reid, JM; Rios, R; Ames, MM;
Indirizzi:
Mayo Clin & Mayo Fdn, Dept Oncol, Div Dev Oncol, Rochester, MN 55905 USA Mayo Clin & Mayo Fdn Rochester MN USA 55905 ncol, Rochester, MN 55905 USA
Titolo Testata:
JOURNAL OF CHROMATOGRAPHY B
fascicolo: 1, volume: 754, anno: 2001,
pagine: 91 - 96
SICI:
1387-2273(20010415)754:1<91:VHLCAF>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
TEMOZOLOMIDE; PHARMACOKINETICS;
Keywords:
dacarbazine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
10
Recensione:
Indirizzi per estratti:
Indirizzo: Reid, JM Mayo Clin & Mayo Fdn, Dept Oncol, Div Dev Oncol, 200 1st St SW, Rochester,MN 55905 USA Mayo Clin & Mayo Fdn 200 1st St SW Rochester MN USA 55905 905 USA
Citazione:
S.L. Safgren et al., "Validated high-performance liquid chromatographic assay for simultaneous determination of dacarbazine and the plasma metabolites 5-(3-hydroxymethyl-3-methyl-1-triazeno)imidazole-4-carboxamide and 5-(3-methyl-1-triazeno)imidazole-4-carboxamide", J CHROMAT B, 754(1), 2001, pp. 91-96

Abstract

Dacarbazine (DTIC) is a prodrug that is clinically effective in the treatment of Hodgkin's disease, melanoma and soft tissue sarcoma. To better characterize the clinical pharmacology of parent drug and reactive metabolites, a reversed-phase HPLC method with UV detection was developed for simultaneous determination of dacarbazine and the metabolites 5-(3-hydroxymethyl-3-methyl-1-triazeno)imidazole-4-carboxamide (HMMTIC) and 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (MTIC). Chromatographic separation was achieved with a Zorbax SB-CN column and with a mobile phase of 80%, 50 mM ammonium phosphate, pH 6.5, 20% methanol and 0.1% triethylamine. HMMTIC, MTIC and DTIC were extracted from plasma with methanol precipitation of the proteins. Recovery of DTIC and the metabolites from whole blood was greater than 92%. Rapid processing of whole blood. methanol extraction and storage at -70 degreesC substantially increased the stability of HMMTIC and MTIC from less than15 min to 3 days. Precision for HMMTIC, MTIC and DTIC ranged from 3.7 to 16.3% relative standard deviation. The accuracy ranged from 101 to 114% for all three analytes. The validated assay was used to determine the pharmacokinetic data for dacarbazine and its active metabolites for human patients with recurrent glioma receiving DTIC intravenously. (C) 2001 Elsevier Science B.V. All rights reserved.

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Documento generato il 15/07/20 alle ore 14:46:19