How versatile is the use of ultrafiltration to study biointeractions of therapeutic metallodrugs?

For a representative number of approved or investigational anticancer metallodrugs varying in lipophilicity, unspecific adsorption onto ultracentrifugal filter units was studied. It was found that for fairly hydrophilic compounds, such as cisplatin and oxaliplatin, the binding to filters does not substantially affect their amount measured (by ICP-MS) after ultrafiltration (>95%). In the case of metal complexes with moderate lipophilicity (log P > −0.1), adsorption effects turn out to be substantial. This might impede using ultrafiltration for studying the transformations of such drugs in human serum, unless they are rapidly converted into the protein adducts. The adsorption-suppressing effect of proteins was proved for indazolium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] whose recovery from the filters was 61 and 14% in free and HSA-bound form, respectively. [Display omitted] •ICP-MS combined with ultrafiltration serves well in metallodrug binding studies.•Adsorption may limit application of ultrafiltration for some metallodrugs.•For hydrophilic cisplatin and oxaliplatin binding to filters is not substantial.•Adsorption effects turn out to be considerable for lipophilic drugs.•Recovery can be improved if a drug is rapidly converted into the protein adducts.