Measurement of surface contamination by certain antineoplastic drugs using high-performance liquid chromatography: applications in occupational hygiene investigations in hospital environments.

Within the context of continuing interest in occupational hygiene of hospitals as workplaces, the authors report the results of a preliminary study on surface contamination by certain antineoplastic drugs (ANDs), recently performed in eight cancer departments of two large general hospitals in Milan, Italy. Since reliable quantitative information on the exposure levels to individual drugs is mandatory to establish a strong interpretative framework for correctly assessing the health risks associated with manipulation of ANDs and rationally advise intervention priorities for exposure abatement, two automated analytical methods were set up using reverse-phase high-performance liquid chromatography for the measurement of contamination by 1) methotrexate (MTX) and 2) the three most important nucleoside analogue antineoplastic drugs (5-fluorouracil 5FU, Cytarabin CYA, Gemcytabin GCA) on surfaces such as those of preparation hoods and work-benches in the pharmacies of cancer wards. The methods are characterized by short analysis time (7 min) under isocratic conditions, by the use of a mobile phase with a minimal content of organic solvent and by high sensitivity, adequate to detect surface contamination in the 5-10 micrograms/m2 range. To exemplify the performance of the analytical methods in the assessment of contamination levels from the target analyte ANDs, data are reported on the contamination levels measured on various surfaces (such as on handles, floor surfaces and window panes, even far from the preparation hood). Analyte concentrations corresponding to 0.8-1.5 micrograms of 5FU were measured on telephones, 0.85-28 micrograms/m2 of CYA were measured on tables, 1.2-1150 micrograms/m2 of GCA on furniture and floors. Spillage fractions between 1-5% of the used ANDs (daily use 5FU 7-13 g; CYA 0.1-7.1 g; GCA 0.2-5 g) were measured on the disposable polythene-backed paper cover sheet of the preparation hood.

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 workplaces, we investigate hospital indoor contamination as a consequence of the use of antineoplastic drugs (ANDs), with the purpose of assessing exposure of medical and nursing personnel to potentially harmful doses of ANDs, and ultimately of yielding advice on safe operating procedures for manipulation of ANDs in hospitals and in house-care of cancer patients. Among the large number of currently employed ANDs, methotrexate (MTX) has been selected as a tracer of surface contamination, on the basis of its wide use in therapy, its ease of measurement and of its chemical properties relevant to persistence and transport in the indoor environment. MTX is a polyelectrolyte, with a high water, but lower organic solvent solubility, a negligible vapour pressure and a high chemical robustness to environmental stress, thus allowing to measure surface-to-surface carryover (e.g. from spillage or glove fingerprint) and indoor contamination due to aerosol transport (e.g. from syringe manipulation procedures). Monitoring of MTX in environmental samples such as swab washings of surfaces and objects requires an analytical method with characteristics of sensitivity, reproducibility, precision, analytical speed, ease of automation and robustness. We have therefore developed an analytical procedure which employs simple short-column RP-HPLC with UV detection, automated sample injection and a close analogue internal standard for improved precision and solid-phase extraction (SPE) for sample concentration. Our method has proven suitable for detecting traces of MTX on a wide variety of surfaces and objects, with a limit of quantification in the range of 50 microg/dm3 for direct injection of unconcentrated washings, corresponding to the possible detection of surface contamination as low as 1 microg/m3 and a limit of detection in the range of 10 ng/m2 for samples as large as 100 dm3 concentrated by SPE. We present preliminary results from a recent hospital case-study, assessing the contamination level of furniture 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 distance from the preparation hoods.

Measurement of surface contamination from nucleoside analogue antineoplastic drugs by high-performance liquid chromatography in occupational hygiene studies of oncologic hospital departments.

Within the frame of a continuing interest in occupational hygiene of hospitals as workplaces, we describe an automated analytical method by reversed-phase high-performance liquid chromatography for the measurement of contamination from the three most important nucleoside analogue antineoplastic drugs (5-fluorouracil, 5FU; cytarabin, CYA; gemcytabin, GCA) on such surfaces as those of preparation hoods and work-benches in departmental pharmacies of oncologic departments. Our method is characterized by a short analysis time (7 min) under isocratic conditions, by the use of a mobile phase devoid of organic solvent and by high sensitivity (LOD > or = 40 micrograms/l for all compounds), adequate to detect surface contamination above a threshold of 4 micrograms/m2 for wide surfaces and of 30 micrograms/m2 for small irregular objects. We present some results from a preliminary survey study recently performed in seven oncologic departments of two large general hospitals in Milan. To exemplify the contamination levels on various surfaces (such as on handles, floor surfaces and window glass panes, even far from the preparation hood), analyte concentrations in the order of 0.03-0.06 microgram/ml, corresponding to 0.8-1.5 micrograms of 5FU were measured on telephones, of 0.02-0.6 microgram/ml (0.85-28 micrograms/m2) of CYA were measured on table boards, of 0.05-10.6 micrograms/ml (1.2-1150 micrograms/m2) of GCA on furniture and floors. Spillage fractions up to 1% of the employed ANDs (employed daily 5FU 7-13 g; CYA 0.1-7.1 g; GCA 0.2-5 g) are measured on the polyethylene-backed paper disposable cover sheet of the preparation hood.