Antineoplastic drugs determination by HPLC/HRMSn to monitor occupational exposure

Occupational exposure to antineoplastic cytostatic drugs has been recognized as a potential health hazard since the seventies. Safety guidelines and recommendations have been published in several countries in order to improve operating procedures and keep exposure levels as low as possible. Nevertheless, contamination still occurs during preparation and administration. The purpose of this study is to develop a simple, direct, multi-residue procedure to evaluate the possible surface contamination of selected antineoplastic drugs in different hospital environment sites by using pads and wipe tests sampling. Carboplatin, 5-fluorouracil, gemcytabine and epirubicin belong to very different chemical classes but all show good ionization properties in electrospray conditions (positive ion mode for epirubicin and negative ion mode in all other cases). LC/MS appears so to be the best technique for direct analysis of these samples (neither derivatization nor complex extraction procedure for polar compounds), together with an high resolution MSn detection that empowers sensitivity. So sample preparation was limited to pads/wipes washing. Chromatographic separation was achieved on C18 reversed phase columns. LOD/LOQ values provide sensitivity good enough to evidence the presence of the drugs in the lowest concentration range (< 1 ng/cm2), where classical determination methods fault. For 5-fluorouracile sensitivity allowed identification of 0.1 pg/cm2 contamination levels without preconcentration of the sample. The method was applied for a study of real pad/wipe tests coming from different areas from an hospital showing 15% of collected samples being positive. Although contamination levels were within described values for similar environment, the low detection limit allows an accurate description of the working environment, description that can be used to define procedural rules to limit working place contamination to a minimum