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.
Hamscher
Gerd
G
Institute of Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, Hannover, Germany. gerd.hamscher@tiho-hannover.de
Mohring
Siegrun A I
SA
Knobloch
Anna
A
Eberle
Nina
N
Nau
Heinz
H
Nolte
Ingo
I
Simon
Daniela
D
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000652:urine*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D003520:Cyclophosphamide / Q000627:therapeutic use / Q000652:urine; D004283:Dog Diseases / Q000188:drug therapy* / Q000652:urine; D004285:Dogs; D004317:Doxorubicin / Q000627:therapeutic use / Q000652:urine; D004350:Drug Residues / Q000032:analysis*; D004781:Environmental Exposure / Q000517:prevention & control; D006282:Health Personnel; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy / Q000662:veterinary; D008415:Mastocytosis / Q000188:drug therapy / Q000662:veterinary; D009369:Neoplasms / Q000188:drug therapy / Q000652:urine / Q000662:veterinary*; D016273:Occupational Exposure / Q000517:prevention & control; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D014747:Vinblastine / Q000627:therapeutic use / Q000652:urine; D014750:Vincristine / Q000627:therapeutic use / Q000652:urine
D000970:Antineoplastic Agents; D014750:Vincristine; D014747:Vinblastine; D004317:Doxorubicin; D003520:Cyclophosphamide