Ultra-performance liquid chromatography coupled with tandem mass spectrometry was used for the biological monitoring of workers occupationally exposed to solvents. The method was developed using a triple quadrupole to investigate the relevant urinary metabolites of styrene, namely mandelic acid and phenylglyoxylic acid. The method provides quantitative and qualitative data to give additional assurance about the nature of the contaminant analyzed in workers' urine. A full scan and a product ion scan were acquired within the chromatographic peak acquired in MRM. For the two metabolites, the repeatability was 96%, the precision ≥97%, and the accuracy ≥93 ± 3%. The quantitative performances were not influenced by the inclusion of simultaneous full scan acquisition as compared to a usual quantitative approach. Footprints of each substance of interest were obtained at each injection, and full scan data can be interrogated for the presence of interferences and other contaminants. The method developed has been submitted to random real samples from both non-occupationally and occupationally exposed workers. The urines of non-occupationally exposed workers were all free of mandelic acid, phenylglyoxylic acid and putative interferences showing the high selectivity of the method. However, the urines of occupationally exposed workers were robustly quantified. The levels of mandelic acid and phenylglyoxylic acid ranged between 0.2 and 9 mM, and the footprints of each metabolite and structural information were acquired in parallel with the quantitative results, thus providing unquestionable data about the nature of the contaminant and the levels reported. The combination of qualitative information acquired simultaneously with quantitative results provides the structural information needed in case of questions, without any harmful effect on the robustness and throughput of the quantitative analysis. Copyright © 2012 John Wiley & Sons, Ltd.