Separation methods for antiviral phosphorus-containing drugs

Among antiviral drugs, phosphorus-containing compounds, foscarnet and cidofovir, present adverse effects including renal toxicity. Since their main therapeutic target is the treatment of CMV retinitis, which needs lifelong maintenance therapy, accurate analytical methods are required for drug monitoring. According to the high hydrophilic property of the two compounds, ion pair reversed-phase HPLC methods were proposed for their separation in drug formulations and biological samples. Their lack of UV absorption at wavelengths above 205 nm does not allow the use of this detection technique for biological fluids. Electrochemical detection methods (coulometry and amperometry) led to a quantification limit of 15 μM for foscarnet. Fluorescent derivatives obtained by modification of cidofovir cytosine nucleus with α-haloketones offered advantage over UV detection and allowed to reach a detection limit of 5 ng/ml, making possible investigations on the drug time-course in biological fluids.