Determination of drug residues in urine of dogs receiving anti-cancer chemotherapy by liquid chromatography-electrospray ionization- tandem mass spectrometry: is there an environmental or occupational risk?

Cytotoxic drugs, previously used only in human medicine, are increasingly utilized for cancer treatment in veterinary practice. We developed and validated a liquid chromatography (LC)-electrospray ionization-tandem mass spectrometry (MS-MS) method to determine vincristine, vinblastine, cyclophosphamide, and doxorubicin in canine urine. Sample pretreatment consisted of liquid-liquid extraction, and LC separation was carried out on an RP C(18) column employing a 0.5% formic acid/methanol gradient system. The analytes were detected in positive ion mode using the MS-MS scan mode. The mean recoveries in six different urine samples were between 64.2% and 86.9%. Limits of quantitation were 0.5 microg/L for vincristine and vinblastine, 1 microg/L for cyclophosphamide, and 5 microg/L for doxorubicin; limits of detection were approximately 0.25 microg/L for vincristine, vinblastine, and cyclophosphamide and 0.5 microg/L for doxorubicin. It could be demonstrated that all investigated drugs are found in urine of dogs undergoing chemotherapy. In samples from day 1 after chemotherapy, as much as 63 microg/L vincristine, 111 microg/L vinblastine, and 762 microg/L doxorubicin could be detected. Cyclophosphamide showed only minor concentrations on day 1, but up to 2583 microg/L could be found directly after chemotherapy. These initial data show that there might be a potential contamination risk when administering cytotoxics in veterinary medicine.