A fully validated simple new method for environmental monitoring by surface sampling for cytotoxics

A wipe sampling procedure followed by a simple ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneous quantification of six cytotoxic drugs: 5-fluorouracil (5FU), doxorubicin (DOXO), epirubicin (EPI), ifosfamide (IF), cyclophosphamide (CP) and gemcitabine (GEM), as surrogate markers for occupational exposure. After a solid-phase extraction of wiping filter on 10 × 10 cm surface, the separation was performed within 6.5 min, using a gradient mobile phase and the analytes were detected by mass spectrometry in the multiple reaction ion monitoring mode. The method was validated according to the recommendations of the US Food and Drug Administration. The method was linear (r² > 0.9912) between 2.5 and 200 ng per wiping sample (25 to 2000 pg/cm²) for 5FU, doxorubicin and epirubicin and between 0.2 and 40 ng per wiping sample (2 to 400 pg/cm²) for cyclophosphamide, ifosfamide and gemcitabine. The lower limits of quantification were 2.5 ng (25 pg/ cm²) for 5FU, doxorubicin and epirubicin, and 0.2 ng (2 pg/cm²) for CP, IF and GEM. Within-day and between-day imprecisions were <14.0, 10.6, 11.1, 8.7, 11.2 and 10.9% for 5-fluorouracil, doxorubicin, epirubicin, ifosfamide cyclophosphamide and gemcitabine, respectively. The inaccuracies did not exceed 2.7, 10.9, 1.1, 4.5, 1.6 and 2.9% for the studied molecules, respectively. This new sensitive validated method for surface contamination studies of cytotoxics was successfully applied on different localizations in hospital. This approach is particularly suitable to assess occupational exposure risk to cytotoxic drugs.