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HPLC methods for determination of two novel thiosemicarbazone anti-cancer drugs (N4mT and Dp44mT) in plasma and their application to in vitro plasma stability of these agents
J. Stariat, P. Kovaříková, J. Klimeš, D.B. Lovejoy, D.S. Kalinowski, D.R. Richardson
Language English Country Netherlands
- MeSH
- Analysis of Variance MeSH
- Financing, Organized MeSH
- Data Interpretation, Statistical MeSH
- Isoniazid analogs & derivatives analysis metabolism MeSH
- Rabbits MeSH
- Humans MeSH
- Naphthalenes blood MeSH
- Swine MeSH
- Antineoplastic Agents blood MeSH
- Pyridoxal analogs & derivatives analysis metabolism MeSH
- Reproducibility of Results MeSH
- Sensitivity and Specificity MeSH
- Drug Stability MeSH
- Thiosemicarbazones blood MeSH
- Chromatography, High Pressure Liquid methods MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Humans MeSH
- Animals MeSH
The aim of this study was to develop and validate HPLC methods for the determination in plasma of two novel thiosemicarbazone anti-tumour drugs developed in our laboratories (Dp44mT and N4mT). The appropriate separations were achieved using a HS F5 HPLC column with the mobile phase composed of a mixture of either acetate buffer/EDTA or EDTA and acetonitrile (62:38 and 50:50, v/v, respectively). The plasma samples were pretreated with SPE (phenyl and C18, respectively). Furthermore, these methods were successfully applied to in vitro plasma stability experiments. The investigation has clearly shown that both thiosemicarbazones are markedly more stable in plasma than their aroylhydrazone forerunners.
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- $a Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic.
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- $a The aim of this study was to develop and validate HPLC methods for the determination in plasma of two novel thiosemicarbazone anti-tumour drugs developed in our laboratories (Dp44mT and N4mT). The appropriate separations were achieved using a HS F5 HPLC column with the mobile phase composed of a mixture of either acetate buffer/EDTA or EDTA and acetonitrile (62:38 and 50:50, v/v, respectively). The plasma samples were pretreated with SPE (phenyl and C18, respectively). Furthermore, these methods were successfully applied to in vitro plasma stability experiments. The investigation has clearly shown that both thiosemicarbazones are markedly more stable in plasma than their aroylhydrazone forerunners.
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