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.
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.
Stariat
Ján
J
Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic.
Kovaríková
Petra
P
Klimes
Jirí
J
Lovejoy
David B
DB
Kalinowski
Danuta S
DS
Richardson
Des R
DR
D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003627:Data Interpretation, Statistical; D004355:Drug Stability; D006801:Humans; D007538:Isoniazid / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D009281:Naphthalenes / Q000097:blood*; D011730:Pyridoxal / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D011817:Rabbits; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013552:Swine; D013882:Thiosemicarbazones / Q000097:blood*
D000970:Antineoplastic Agents; C540034:N4mT agent; D009281:Naphthalenes; D013882:Thiosemicarbazones; C539263:di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone; D011730:Pyridoxal; C021079:pyridoxal isonicotinoyl hydrazone; D007538:Isoniazid