Dispersive solid‐phase extraction procedure coupled to UPLC‐ESI‐MS/MS analysis for the simultaneous determination of thirteen cytotoxic drugs in human urine

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.