Quantification of five antineoplastic agents in swab samples using UPLC-ESI-MS/MS: Method development and validation.

BACKGROUND

Antineoplastic agents are hazardous drugs used in cancer treatment and consequently can be present at the workplace (e.g. hospital), but also in a home-setting in case of treatment at home. Given the serious health effects, it is important to monitor environmental contamination on a regular base. As currently, no method allows for simultaneous quantification of cyclophosphamide, etoposide, mitomycin C, imatinib and 5-fluorouracil, we developed and validated a method for simultaneous quantification of multiple antineoplastic agents in swab samples.

RESULTS

Sample collection was optimised and samples were extracted using solely an extraction solvent (water or water/acetonitrile), shaking and sonicating. Ultra performance liquid chromatography coupled to tandem mass spectrometry with electrospray ionisation was used for detection of the compounds. Selectivity, linearity, sensitivity, precision and accuracy were determined. The LLOQs were 0.3 ng/swab (cyclophosphamide, mitomycin C), 1 ng/swab (etoposide) and 5 ng/swab (imatinib, 5-fluorouracil). After a spill, quantifiable concentrations of antineoplastic agents could be measured in swabs using the developed methods. After cleaning, all concentrations fell below the LLOQ.

SIGNIFICANCE: Two methods allowing for safe collection, rapid preparation and sensitive quantification were developed and can be applied in the field to measure environmental contamination. One for simultaneous quantification of cyclophosphamide, etoposide, mitomycin C and imatinib, one for quantification of 5-fluorouracil.