Simultaneous detection of three antineoplastic drugs on gloves by liquid chromatography with diode array detector

Abstract

The aim of this study was to develop a method for simultaneous detection of antineoplastic drugs on gloves since, in occupational exposure, the main contamination route is through dermal contact, which may occur via prolonged contact with contaminated surfaces or materials. The assay was performed by liquid chromatography using the following conditions for the detection of 5-fluorouracil (5-FU), methotrexate (MTX) and paclitaxel (TAX): diode array detection and UV quantification at 195 nm for TAX, at 265 nm for 5-FU and at 302 nm for MTX; ODS column (250 x 4 mm, 5 µm) with a similar guard column; mobile phase consisted of water (pH 4)-methanol-acetonitrile (35:15:50, v/v/v) with a flow rate of 1 mL min -1 . The method presented a linear range from 0.25 to 20 µg mL -1 with r 2 higher than 0.99. Repeatability was ≤15% and satisfactory extraction efficiency was obtained when liquid-liquid extraction with ethyl acetate was used for 5-FU and TAX. Satisfactory solid phase extraction was also achieved with C18 cartridges and elution with methanol for MTX. The diode array detector allowed drug quantification at a concentration ≥ 0.25 µg mL -1 in samples, although detection was possible in samples that presented values of around 0.1 µg mL -1 . The results obtained suggest that the method developed can be applied for the simultaneous determination of the drugs studied and can be considered useful in exposure assessment for health care workers.Uniterms: Antineoplastic drugs/detection. Gloves/toxicologial analysis. High Performance Liquid Chromatography/toxicologial analysis. Occupational exposure.O objetivo deste estudo foi desenvolver um método para a detecção simultânea de antineoplásicos em luvas, uma vez que, em exposições ocupacionais, a principal via de introdução é a dérmica, por meio de contato prolongado com superfícies e/ou materiais contaminados com tais fármacos. A tecnica de detecção utilizada foi a cromatografia líquida de alta eficiência, com detector de aranjo de diodos, nas seguintes condições: para a detecção de 5-fluorouracila (5-FU), metotrexato (MTX) e paclitaxel (TAX): detecção e quantificação de TAX a 195 nm, de 5-FU a 265 nm e de MTX a 302 nm; coluna ODS (250 x 4 mm, 5 mm), com pré-coluna similar; fase móvel constituída de água (pH 4)-metanol-acetonitrila (35:15:50, v/v/v), na vazão de 1 mL min -1. O método apresentou uma faixa linear de 0,25-20 mg mL -1 , com r 2 > 0,99. O desvio-padrão relativo, para a avaliação da repetibilidade foi ≤ 15%; a recuperação foi satisfatória, empregando extração líquido-líquido, com acetato de etila, para a 5-FU e TAX e extração em fase sólida, com cartuchos de C18 e eluição com metanol, para MTX. O detector de arranjo de diodos permitiu a quantificação dos fármacos, quando presentes nas amostras em concentração ≥ 0,25 mg mL -1 , embora a detecção foi possível nas amostras que apresentaram valores em torno de 0,1 mg mL -1 . Os resultados obtidos sugerem que o método desenvolvido pode ser aplicado para a determinação simultânea dos fármacos estudados, constituindo ferr...

Residual contamination in antineoplastic drug packaging

“…1 In addition, antineoplastic drugs have been shown to have carcinogenic, mutagenic, teratogenic, and genotoxic effects in humans. 2–6…”

Second derivative spectrophotometric determination of cyclophosphamide in pharmaceutical formulations

“…Several analytical methods have been reported and published for quantitative determination of CP in biological fluid and environmental samples, such as: High performance liquid chromatography (HPLC) methods (Malothu et al, 2009;Ahmad et al, 2011), gas chromatography (GC)-mass spectrometry (Sugiura et al, 2010), and after extraction of CP by solid phase extraction techniques, using solid-phase extraction and GC-MS spectrometry (Martins et al, 2004), on-line sample preparation method by micro-extraction packed sorbent (MEPS) followed by LCMS/MS (Kamel et al, 2009), liquid chromatography with diode array detector (Alcântara et al, 2010), and spectrophotometric method (Karen et al, 2009). To our knowledge, there are no derivative spectrophotometric methods concerning the determination of cyclophosphamide in pharmaceutical formulations.…”