High-performance liquid chromatography of methotrexate for environmental monitoring of surface contamination in hospital departments and assessment of occupational exposure

In the frame of applicative research in occupational hygiene of hospital wo rkplaces, we investigate hospital indoor contamination as a consequence of the use of antineoplastic drugs (ANDs), with the purpose of assessing expos ure of medical and nursing personnel to potentially harmful doses of ANDs, and ultimately of yielding advice on safe operating procedures for manipula tion of ANDs in hospitals and in house-care of cancer patients. Among the l arge number of currently employed ANDs, methotrexate (MTX) has been selecte d as a tracer of surface contamination, on the basis of its wide use in the rapy, its ease of measurement and of its chemical properties relevant to pe rsistence and transport in the indoor environment, MTX is a polyelectrolyte , with a high water, but lower organic solvent solubility, a negligible vap our pressure and a high chemical robustness to environmental stress, thus a llowing to measure surface-to-surface carryover (e.g. from spillage or glov e fingerprint) and indoor contamination due to aerosol transport (e.g. from syringe manipulation procedures). Monitoring of MTX in environmental sampl es such as swab washings of surfaces and objects requires an analytical met hod with characteristics of sensitivity, reproducibility, precision, analyt ical speed, ease of automation and robustness. We have therefore developed an analytical procedure which employs simple short-column RP-HPLC with UV d etection, automated sample injection and a close analogue internal standard for improved precision and solid-phase extraction (SPE) for sample concent ration. Our method has proven suitable for detecting traces of MTX on a wid e variety of surfaces and objects, with a limit of quantification in the ra nge of 50 mu g/dm(3) for direct injection of unconcentrated washings, corre sponding to the possible detection of surface contamination as low as 1 mu g/m(3) and a limit of detection in the range of 10 ng/m(2) for samples as l arge as 100 dm(3) concentrated by SPE. We present preliminary results from a recent hospital case-study, assessing the contamination level of furnitur e and equipment in drug preparation areas. Spillage fractions as high as 5% of the employed mass (70-260 mg/day) are measured on the polythene-backed paper disposable hood cover sheet; traces of MTX in the microgram range can also be measured on floor surfaces, furniture and handles, even at a dista nce from the preparation hoods. (C) 1999 Published by Elsevier Science BN. All rights reserved.