Dicationic ion-pairing of phosphoric acid diesters post-liquid chromatography and subsequent determination by electrospray positive ionization-tandem mass spectrometry

Several organophosphate triesters are widely used as flame retardants and can be metabolized to dibutyl (DBP), diphenyl (DPhP), di(2-ethylhexyl) (DEHP) and di(1,3-dichloro-2-propyl) (or bis(1,3-dichloro-2-propyl); DDCPP) phosphoric acid, respectively. A highly sensitive liquid chromatography–electrospray ionization(+)-triple quadrupole mass spectrometry (LC–ESI(+)-QQQ-MS/MS) based analysis method was presently developed. In this method the target compounds were separated with a C18-based reversed phase LC column, and decamethonium hydroxide (dicatonic reagent) was introduced post-LC to form ion-pairs, which were subsequently detected by ESI(+). For the phosphate acid diester ion-pairs, the mass spectra showed the most abundant ion to be [(CH3)2N(CH2)10N(CH3)3]+, with lesser abundances of [[M−H]−[(CH3)3N(CH2)9CH2]2+]+ and [CH2CH(CH2)8N(CH3)3]+. For DDCPP, the fragment ions of [[Cl]−[(CH3)3N(CH2)10N(CH3)3]2+]+ and [[Cl]−[(CH3)3N(CH2)9CH2]2+]+ could also be observed. The limits of quantitation (LOQs) by LC–ESI(+)-MS/MS (based on multiple reaction monitoring) were 0.14, 0.03, 0.14 and 0.02 ng/mL for DPhP, DBP, DDCPP and DEHP, respectively. The response was highly linearly correlated (r > 0.995) with concentration over the range of the LOD to 1000 ng/mL. The matrix effect on ESI+ was negligible for the samples in experiment of in vitro metabolism using rat liver microsomes.

► Phosphoric acid diesters (PADs) were determined by ion-pairing post-LC with decamethonium dication.
► Cationic ion-paired molecular ions were dominant in the ESI(+)-Q-ToF-MS mass spectra.
► A unique quantitative, LC–ESI(+)-QQQ-MS/MS-based method was developed.
► PAD-ion-pair cation sensitivity was higher relative to direct PAD anion analysis.
► Highly sensitive determination of PAD-ion-pairs is possible for a larger suite of PADs.