title: Dispersive solid-phase extraction procedure coupled to UPLC-ESI-MS/MS analysis for the simultaneous determination of thirteen cytotoxic drugs in human urine.
abstract: A fast and easy tailored dispersive solid-phase extraction (d-SPE) procedure has been developed for the determination of 13 cytostatic drugs. Combined with a rapid and simultaneous ultra performance liquid chromatography/tandem mass spectrometry method for residue identification and quantification in urine, it has been fully validated and tested to study a realistic situation in working environment. The target compounds were chosen from the most common classes used in hospitals. The d-SPE adsorbent was obtained mixing Oasis HLB® with C18 and applied to a large volume of sample (10 mL). The electrospray ionization-mass spectrometry acquisition was conducted in a mixed period mode: six acquisition windows were in positive ionization and one in negative (for 5-fluorouracil). The lowest limit of quantification was found at 0.04 μg/L urine for methotrexate. The absolute recovery of cytotoxic drugs was assessed at two concentrations levels and ranged from 67.1% (cytarabine) to 102.3% (etoposide) and from 65.3% (cytarabine) to 101.2% (methotrexate) for the lower and higher levels, respectively, with the relative standard deviation always <12%. This method gives the opportunity to analyze drugs in a wide molecular weight range (from 130 to 853 a.m.u.) and in a complex matrix, such as urine, without losing any of the features that a method intended for trace quantification must have. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Italian Workers' Compensation Authority, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, Chemical Agents Laboratory, Via Fontana Candida 1, 00040, Monte Porzio Catone, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fabrizi
authors.affiliation: Italian Workers' Compensation Authority, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, Chemical Agents Laboratory, Via Fontana Candida 1, 00040, Monte Porzio Catone, Rome, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Fioretti
authors.affiliation: Italian Workers' Compensation Authority, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, Chemical Agents Laboratory, Via Fontana Candida 1, 00040, Monte Porzio Catone, Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Mainero Rocca
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000652:urine*; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D052616:Solid Phase Extraction / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents
keywords: UPLC-MS/MS; antineoplastic drugs; dispersive SPE; occupational exposure; urine analysis