Rapid non-separative determination of prevailing organophosphate flame retardants metabolites in urine by means of a restricted access material coupled to tandem mass spectrometry

• BDCPP and DPhP determination in human urine in less than 5 min. • The combination of RAM and MS/MS avoid the need for a chromatographic separation. • Validated with certified urine samples (86%-108% accuracy). Organophosphate flame retardants (OPFRs) are used to reduce the flammability of various materials. Among these compounds, triphenyl phosphate (TPhP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) are prominent OPFRs associated with reproductive and endocrine-disrupting effects. Monitoring their urinary metabolites, diphenyl phosphate (DPhP) and bis(1,3-dichloro-2-propyl) phosphate (BDCPP), are crucial for assessing bioaccumulation, toxicity, and exposure. This study presents a novel, non-separative analytical method combining restricted access material (RAM) with tandem mass spectrometry (MS/MS), eliminating the need for chromatographic separation. This innovation significantly reduces total analysis time down to less than five minutes per sample (12 samples per hour), compared to up to 37 min (only one sample per hour) required by state-of-the-art separative methods. The method achieves sub-ppb limits of quantification (LOQ ≤ 0.1 ng mL −1 ) that are equal or better than those achieved by separative methodologies. Matrix effects were minimized (≃20 %) with a conventional clean-up pretreatment based on SPE. The whole methodology was validated by analyzing certified urine samples provided by Centre de toxicologie du Québec and applied to the analysis of real urine samples from non-exposed individuals. The accuracy (86–108 %), precision (RSD < 20 %) and high recovery (98–109 %) confirm the robustness and suitability of this method in routine laboratory applications. This is the first report, to the best of our knowledge, to fully integrate RAM with direct MS/MS analysis for most prominent urinary OPFR metabolites without chromatographic separation. This methodological advance offers substantial advantages in speed, simplicity, and adaptability to high-throughput biomonitoring studies, setting a new benchmark for the determination of DPhP and BDCPP in human urine.