Method validation for quantification of five antineoplastic agents in urine using UPLC-ESI-MS/MS

Antineoplastic agents are hazardous compounds frequently used in cancer treatment. It is already known that the hospital environment poses a risk of occupational exposure to these agents. However, recent years, the rise of outpatient treatment and at-home treatment has introduced an additional risk including also cohabitants of patients. We identified a clear need for highly sensitive monitoring methods to assess exposure to high-risk compounds in a home setting. This study presents two validated methods for quantifying five high-risk antineoplastic agents in urine: one for cyclophosphamide, etoposide, mitomycin C and imatinib, and one for alpha-fluoro-beta-alanine. Liquid-liquid extraction with ethyl acetate was used for extraction of cyclophosphamide, etoposide, mitomycin C and imatinib from urine. Alpha-fluoro-beta-alanine was extracted using solid-phase extraction with Oasis HLB cartridges. All samples were analysed using ultra-performance liquid chromatography coupled to tandem mass spectrometry. During method validation, selectivity, extraction efficiency, matrix effect, process efficiency, linearity, sensitivity, precision and accuracy were established. The lower limits of quantification were determined to be 0.1 ng/mL (cyclophosphamide and mitomycin C), 0.7 ng/mL (etoposide), 1 ng/mL (alpha-fluoro-beta-alanine) and 10 ng/mL (imatinib). The methods were fully validated and are now ready for application in the field.