Desenvolvimento de métodos para a determinação simultânea de antineoplásicos em superfícies e luvas visando a aplicação na monitorização da exposição ocupacional

Abstract

Therapeutic importance and benefits obtained from antineoplastic drugs are unquestionable. However, their side effects are not well-known and extensive use and exposure to multiple agents may put health care workers involved in the preparation and administration of these drugs at risk. Therefore, it is important to have accurate methods for simultaneous analysis and evaluation of the occupational exposure. The aim of this study was to develop methods for simultaneous determination of antineoplastics in surfaces and gloves since, in the occupational exposure, the main contamination route is dermal contact, which may occur by prolonged contact with contaminated surfaces or instruments/materials. The assay was performed by High Performance Liquid Chromatography (HPLC) and the optimized conditions for 5-fluorouracil (5-FU), methotrexate (MTX), doxorrubicin (DOX), cyclophosphamide (CP) and ifosfamide (IFO), in surface samples, were: detection in 195 nm, C18 column (5 μm, 250 x 4 mm) with a similar guard column; mobile phase was constituted by water, pH 4: methanol: acetonitrile (70:13:17, v/v/v) with a flow of 0.4 mL min-1 up to 13 minutes and after this 1 mL min-1 and cleaning of surfaces with acetonitrile: methanol (50:50), without previous extraction. The method presented a linear calibration range from 0.25 to 20 μg mL-1 for 5-FU and MTX and from 0.5 to 20 μg mL-1 for IFO, DOX and CP with determination coefficients (r2) higher than 0.99. The repeatability, expressed in terms of percent relative standard deviation was 11% and extraction efficiency ranged from 74 to 106%. Optimized conditions for 5-FU, MTX and paclitaxel (PAC), in gloves, were: diode array (DAD) detection and UV quantification in 195 nm to PAC, 265 nm to 5-FU and 302 nm to MTX; C18 column (5 μm, 250 x 4 mm) with a similar guard column; mobile phase was constituted by water, pH 4: methanol: acetonitrile (35:15:50, v/v/v) with a flow of 1 mL min-1. The method presented a linear calibration range from 0.25 to 20 μg mL-1 with determination coefficients (r2) higher than 0.99. Extraction efficiency was between 71 to 115% and repeatability, expressed in terms of percent relative standard deviation was 15% and satisfactory extraction efficiency was obtained when liquid extraction, with ethyl acetate, was used for 5-FU and PAC and solid phase, with C18 cartridges and elution with methanol, for MTX. DAD detector allowed drugs detection at concentration below 0.25 μg mL-1, in glove samples. The results obtained suggest that the developed methods can be applied for simultaneous determination of the drugs studied and are considered useful in exposure assessment for health care workers.