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A potentiometric titration technique has been used to determine the stability constants for the various complexes of Co(II) and Cu(II) with L-asparagine and from DNA base, e.g. adenine. Stability constants of ternary systems have been evaluated by the method suggested by IrwingRossotti. In addition, the conditional constants were calculated as a function of pH. The maximum values of the conditional formation constants were found to be in accordance with the mixed-ligand complex formation constants in a determined pH region. Furthermore, the molar fractions of different species from mixed complexes were calculated by means of formation constants. The values of stability constants of mixed-ligand complexes at 25°C are as follows: log K= 5.25 for Co(II)-L-asparagine-adenine; log K= 9.30 for Cu(II)-L-asparagine-adenine. The ionic strength was kept constant at I = 0.20 with NaClO 4 .

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In the present study, the stability constants of the complexes which were formed from N-benzylideneaniline (BDA), N-benzylidene-4-chloroaniline (BDCA), N-(4-chlorobenzylidene)aniline (CBDA), N-benzylidene-4nitroaniline (BDNA) and N-benzylidene-4-hydroxyaniline (BDHA) with chromium (III), manganese (II), cobalt (II), nickel (II), copper (II), zinc (II)and cadmium (II) were determined potentiometrically by using CalvinBjerrum and Irving-Rossotti methods. The protonation constants and dissociation constants of the ligands were found at 25°C and for 1=0,11 are given below:BDA logK, = pK, = 4,36 ; BDCA logK, = pK, = 3,60 ;CBDA logK, = pK, = 4,56 ; BDNA logK, = pK, = 2,45;BDHA logK, = pK 2 = 11,05 ; logK 2 = pK, = 5,75The formation constants of complexes formed using Cr(III), Mn(ll), Co(Il), Ni(ll), Cu(ll), Zn(II), Cd(II) are, respectively, 3.50; 3.90; 3.21; 3.90; 2.99; 3.30 and 3.30 for BDA; 3.35; 3.05; 3.05; 2.89; 2.93; 2.88 and 2.89 for 4.90; 5.26; 11.00; 6.52 and 4.40 for BDHA. None of these metals formed complexes with BDNA.The conditional formation constants and the pH ranges of formation of the resulting complexes were determined. The relative abundance was plotted using conditional formation constants of the complexes and the steps for the formation of the complexes were shown in graphs. The composition of metal complexes for monodentate ligands was determined as a metal/ligand ratio of 1:1. The composition of chromium and copper complexes for bidentate ligands was determined as a metal/ligand ratio of 1:2, while the ratio of other metal complexes was 1:1.

The use of infusional chemotherapy, especially in an ambulatory setting, absolutely requires that the individual agents remain stable in solution at room temperature and that the drugs be compatible. Because of this, investigation of the chemical compatibilities of chemotherapeutic drug combinations given in the same infusion solution is quite important especially if the drugs are to remain in solution for long periods. Thus, the visual and chemical compatibility of irinotecan and epirubicin in the same infusion solution were investigated using both reference standards and pharmaceutical dosage forms. No sign of incompatibility was observed upon visual examination by means of effervescence, pH change, precipitation and colour change. But a chemical incompatibility was observed using a spectrophotometric method in the spectra of irinotecan-HCl and epirubicin-HCl. The molar ratio of epirubicin-HCl/irinotecan-HCl at which the interaction reached a maximum was found to be 2:1. The chemical interaction occurred immediately after admixing and no visual or spectral change was noticed for 24 h after the interaction had occurred. It is concluded that these drugs are chemically incompatible. While the applicability of these two drugs in combination is investigated in further pharmacological studies, their chemical interaction should also be a consideration. The positive or negative contribution of this interaction to the pharmacological effect of the combination might be of importance, and therefore should be investigated in further clinical trials.