Simultaneous biomonitoring of 15 organophosphate flame retardants metabolites in urine samples by solvent induced phase transition extraction coupled with ultra-performance liquid chromatography-tandem mass spectrometry

Abstract

Organophosphate flame retardants and plasticizers (OPFRs) are widely additives in consumer products and building materials. They are frequently detected in environmental media, including indoor air, water, soil, and dust. To provide a low-cost and multi-target tool for monitoring individual exposure to OPFRs, a high-throughput method for simultaneous detection of 15 urinary OFPR metabolites was established using solvent induced phase transition extraction (SIPTE) technique for sample pretreatment and ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) for target quantification. SIPTE is implemented by adding a hydrophobic solvent (methyl tert-butyl ether, used as the phase transition solution) to the homogeneous acetonitrile (ACN) aqueous solution for phase separation. Method performance was validated based on the evaluation indicators. The linear range of this present method was between 0.1 and 50 ng/mL for 15 urinary OPFR metabolites. The limits of detection (LODs) were from 0.012 to 0.25 ng/mL, and the spiked recoveries ranged of 71.3–117.6%, with corresponding relative standard deviations (RSDs) from 4.8 to 25.6%. Unlike most studies only focused on the determination of dialkyl and diaryl phosphate esters (DAPs), our analytical method also covered hydroxylated OPFRs metabolites (OH-OPFRs). Seven DAPs with detection frequencies (DF) more than 60% were detected in a small pilot study (n = 15). Besides, 4-hydroxy diphenyl phosphate (4-HO-DPHP) could be also detected in urine samples. Overall, this newly developed high-throughput analytical method could simultaneously determine 15 urinary OPFRs metabolites and screen these biomarkers of human exposure to OPFRs.