Fast methodology for the reliable determination of nonylphenol in water samples by minimal labeling isotope dilution mass spectrometry

• In-house synthesis and characterization of the isotope-marked compound 13C1-4-(3,6-dimethyl-3-heptyl)phenol (13C1-363 NP).
• Determination of technical mixture of nonylphenol combining minimal labeling and isotope pattern deconvolution.
• Fully validation of the proposed SPE–UHPLC–MS/MS methodology in bottled water, effluent wastewater and influent wastewater.
• Suitable correction of matrix effect using 13C1-363 NP as surrogate.
• Study of the lack of suitability of n-nonylphenol as internal standard in wastewaters.

In this work we have developed and validated an accurate and fast methodology for the determination of 4-nonylphenol (technical mixture) in complex matrix water samples by UHPLC–ESI-MS/MS. The procedure is based on isotope dilution mass spectrometry (IDMS) in combination with isotope pattern deconvolution (IPD), which provides the concentration of the analyte directly from the spiked sample without requiring any methodological calibration graph. To avoid any possible isotopic effect during the analytical procedure the in-house synthesized 13C1-4-(3,6-dimethyl-3-heptyl)phenol was used as labeled compound. This proposed surrogate was able to compensate the matrix effect even from wastewater samples. A SPE pre-concentration step together with exhaustive efforts to avoid contamination were included to reach the signal-to-noise ratio necessary to detect the endogenous concentrations present in environmental samples. Calculations were performed acquiring only three transitions, achieving limits of detection lower than 100 ng/g for all water matrix assayed. Recoveries within 83–108% and coefficients of variation ranging from 1.5% to 9% were obtained. On the contrary a considerable overestimation was obtained with the most usual classical calibration procedure using 4-n-nonylphenol as internal standard, demonstrating the suitability of the minimal labeling approach.