REVERSED-PHASE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY OF 4-(2-PYRIDYL)-1-PIPERAZINETHIOCARBOXYLIC ACID 2-[1-(PYRIDYL)ETHYLIDENE]HYDRAZIDE DIHYDROCHLORIDE (NSC-348977), A SYNTHETIC THIOSEMICARBAZONE WITH ANTITUMOR-ACTIVITY

Reversed-phase HPLC conditions for the separation of 4-(2-pyridyl)-1-p iperazinethiocarboxylic acid 2-[1-(pyridyl)ethylidene]hydrazide dihydr ochloride (NSC 348977, I), a synthetic thiosemicarbazone with antitumo r activity, from mouse plasma have been investigated. Following denatu rization and precipitation of the spiked plasma with acetonitrile, an aliquot of the supernatant was diluted with aqueous buffer and subject ed to analysis on a Nova-Pak C-18 column (150x3.9 mm I.D.) by isocrati c elution with 50 mM aqueous potassium phosphate buffer (pH 6.8, conta ining 1 mM EDTA)-acetonitrile (60:40, v/v). The column effluent was mo nitored for UV absorption at 310 nm. Problems identified in the sample preparation and separation of I include sensitivity to oxygen, light, non-neutral pH and the presence of metal ions. These factors were see n to adversely influence sample recovery, and attempts were made to fi nd conditions which minimize their effects. (C) 1998 Elsevier Science B.V.