Liquid chromatography coupled to tandem mass spectrometry for the residue determination of ethylenethiourea (ETU) and propylenethiourea (PTU) in water

Abstract

Ethylenethiourea (ETU) and propylenethiourea (PTU) are the main degradation products of dithiocarbamates fungicides, which are widely used in agriculture from several years ago. Their determination in water at low concentrations (e.g. sub-ppb levels) is highly problematic due to their polar character and low molecular size. In the present study, two analytical methodologies have been developed and compared for the selective and sensitive determination of ETU and PTU in various types of waters. Both approaches are based on liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with electrospray ionization, using triple quadrupole analyzer. Whereas the first methodology used an on-line solid-phase extraction (SPE) step in order to reach the adequate sensitivity, the second one avoided sample treatment and was based on direct injection into an ultra high performance liquid chromatography (UHPLC-MS/MS) system, making use of a new-generation instrument in order to reach sub-ppb analyte levels in water. Strong matrix effects (typically leading to signal enhancement) were observed for most of the evaluated waters, especially when applying the on-line SPE method, surely due to the higher amount of sample injected into the system. The use of the own analyte (ETU-d₄)) as isotope-labelled internal standard (ILIS) allowed to compensate these effects and to achieve an accurate ETU quantification at low concentrations. Moreover, three simultaneous transitions, operating in selected reaction monitoring mode, were acquired for both ETU and ETU-d₄. This fact together with the evaluation of their relative intensity ratios assured the reliable identification of the analyte in the water samples. The two optimized methodologies were validated by analysis of six different samples (two drinking water, two groundwater and two surface water), spiked at two levels (0.1 and 1.0 μg/L), and analyzed each in quintuplicate. Satisfactory accuracy and precision, with recoveries ranging from 73 to 104% and RSDs lower than 20%, were obtained for ETU. Limits of detection for ETU were found to be 0.058 μg/L and 0.027 μg/L with direct injection and with the on-line methodology, respectively. No satisfactory recoveries were obtained, in general, for PTU despite using its own deuterium-labelled molecule for matrix effects correction. Notable differences in the chemical behaviour between PTU and PTU-d₆ were observed, which lead to significant variation in their chromatographic retention time and ionization efficiency. Thus, no satisfactory correction of matrix effects could be reached illustrating that the use of deuterated ILIS can be problematic in some particular cases. Despite the poor correction, a semi-quantitative analysis would be feasible for PTU at sub-ppb levels in water. To the best of our knowledge, this is the first article reporting the use of LC-MS/MS for the trace level determination of these problematic analytes in water.

Investigation of pharmaceutical metabolites in environmental waters by LC-MS/MS

“…It is interesting to notice that the ILIS 233 carbamazepine 10,11-epoxide-d 10 did not fully correct matrix effects for its own analyte. Similar 234 situation has been reported for some labelled compounds with a high degree of deuterated atoms 235 (Ripollés et al 2012). It seems that the isotope-labelled compound and the analyte had different 236 physico-chemical behaviour, leading to an (unexpected) unsatisfactory correction.…”

Comparison of different methods aiming to account for/overcome matrix effects in LC/ESI/MS on the example of pesticide analyses

“…This may lead to similar problems as with structural analoguesthe matrix compounds co-eluting with the sample are different resulting in different ionisation suppression. For example Ripolles et al 38 showed that propylenethiourea could not be determined with adequate recovery as the corresponding isotope-labelled (d 6 ) IS showed signicantly different chemical properties from the analyte (e.g. retention time, ionization behaviour).…”

Multi-class determination of personal care products and pharmaceuticals in environmental and wastewater samples by ultra-high performance liquid-chromatography-tandem mass spectrometry

“…The use of the own analyte ILIS is surely the best option for satisfactory correction in all sample types, but this assumption would need to be supported by experimental data as some labelled compounds (e.g. high degree of deuterated isotopes) can have different physico-chemical behavior than the analyte [26]. In multi-residue methods, it uses to be unpractical to correct each compound with its own ILIS due to the high cost and the low commercial availability of ILIS reference standards.…”