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.

Determination of oxaliplatin enantiomers at attomolar levels by capillary electrophoresis connected with inductively coupled plasma mass spectrometry.

The aim of this study was to develop a method for the separation of oxaliplatin enantiomers at attomolar concentration levels. A combination of capillary electrophoresis and inductively coupled plasma mass spectrometry was chosen due to their unique characteristics, including fast and easy modification of separation selectivity, and significant limits of detection and linearity. In the first step, we optimized conditions for the separation of oxaliplatin enantiomers including background electrolyte composition and concentration, pH, and type and concentration of the chiral selector. Under optimal conditions, sodium borate buffer pH 9.5, ionic strength 40 mmol L-1, with 60 mg mL-1 sulfated ß-cyclodextrin, separation was obtained with a resolution of 2.0. This electrolyte system was then used in the 'in-house' connection of capillary electrophoresis with inductively coupled plasma mass spectrometer. In this instance, separation lasted for 9.5 min. Calibrations were linear in the range of 0.1-500 µg mL-1 with R2 of 0.9999. LOD and LOQ values were of 64 ng mL-1 and 116 ng mL-1 of oxaliplatin, respectively. This represents detection of 49 fg or 125 attomol of oxaliplatin enantiomers in the capillary electrophoresis injected sample zone. Finally, the method was successfully applied for detection of oxaliplatin enantiomers in spiked urine samples.