Development and validation of an LC–MS/MS procedure for environmental monitoring of eight cytostatic drugs in pharmacies

Abstract

Abstract An LC–MS/MS multi-method for the simultaneous determination of the structurally different and frequently used cytostatic drugs 5-fluorouracil, gemcitabine, methotrexate, cyclophosphamide, ifosfamide, etoposide, docetaxel and paclitaxel was developed and validated. In order to perform repeated ambient monitoring in 130 German pharmacies all steps of the monitoring procedure such as sample collection, transport, storage, sample preparation and HPLC–MS/MS analysis have been adapted and optimised. Thus sensitivity and reliability as well as sample throughput were increased. The final method consists of wipe sampling from 900 cm2 surfaces and extraction of the tissues with an aqueous pH 3 solution. The limits of quantification range from 3.7 to 37 pg cm−2. Validation showed that sampling via the individual pharmacy personnel does not affect the overall results. Recovery rates below 70% were observed on rough surfaces for the taxanes docetaxel and paclitaxel. Likewise, neither the storage nor the shipping conditions affected the results significantly. Keywords: liquid chromatography mass spectrometrycytostatic drugswipe samplesenvironmental monitoringoccupational exposuresurface contamination Acknowledgements Special thanks to Christiane Balden and Helmut Graewe (IUTA) for their excellent technical help. Andrea Boergers, Ina Strzysch, Carsten von Bonn, Steffen Wiese and Marco Zedda are gratefully acknowledged for visiting all pharmacies and training the sampling procedure to all study participants. In addition we thank all involved employees and students of IUTA for their contributions to the study. The personnel of the investigated pharmacies are especially acknowledged for their effort and patience during MEWIP.