A QuEChERS-based UPLC-MS/MS method for rapid determination of organophosphate flame retardants and their metabolites in human urine

Organophosphate flame retardants (OPFRs) have been widely used in consumer products to prevent fire spread. However, once released into the atmospheric environment, they may accumulate in humans and undergo metabolic transformation and excretion by urine. In order to clarify the human exposure to OPFRs, a quick, easy, cheap, effective, rugged, and safe method for the simultaneous determination of urinary OPFRs and their metabolites by ultra-performance liquid chromatography-tandem triple quadrupole mass spectrometry was developed. After the optimization by a single-factor or orthogonal experiment, the satisfactory recovery (87.8-119%), matrix effect (-8.88-9.29%), method quantitation limit (3.66-159 ng/L), and inter-day repeatability (1.24 - 10.6%) of most analytes were achieved in artificial urine samples. Based on a monitoring test by the developed method, we propose that urinary bis(1-chloro-2-propyl) phosphate and di-p-cresyl phosphate could be used to trace human exposure to tris(1-chloro-2-propyl) phosphate and tricresyl phosphate, respectively. Most importantly, this is the first study to reveal that 4-hydroxyphenyl diphenyl phosphate (4-OH-TPHP) was dominantly presented in its conjugated form rather than its free form in urine (p = 0.037). Overall, the obtained results contribute a relatively rapid method to help conduct large-scale urine monitoring for revealing the human exposure and risk of OPFRs.