In matrix derivatization of trichloroethylene metabolites in human plasma with methyl chloroformate and their determination by solid-phase microextraction–gas chromatography-electron capture detector

Trichloroethylene (TCE) is a common industrial chemical that has been widely used as metal degreaser and for many industrial purposes. In humans, TCE is metabolized into dichloroacetic acid (DCA), trichloroacetic acid (TCA) and trichloroethanol (TCOH). A simple and rapid method has been developed for the quantitative determination of TCE metabolites. The procedure involves the in situ derivatization of TCE metabolites with methyl chloroformate (MCF) directly in diluted plasma samples followed by extraction and analysis with solid-phase microextraction (SPME) coupled to gas chromatography-electron capture detector (GC-ECD). Factors which can influence the efficiency of derivatization such as amount of MCF and pyridine (PYR), ratio of water/methanol were optimized. The factors which can affect the extraction efficiencies of SPME were screened using 27−4 Placket–Burman Design (PBD). A central composite design (CCD) was then applied to further optimize the most significant factors for optimum SPME extraction. The optimum factors for the SPME extraction were found to be 562.5 mg of NaCl, pH at 1 and an extraction time of 22 min. Recoveries and detection limits of all three analytes in plasma were found to be in the range of 92.69–97.55% and 0.036–0.068 μg mL−1 of plasma, respectively. The correlation coefficients were found to be in the range of 0.990–0.995. The intra- and inter-day precisions for TCE metabolites were found to be in the range of 2.37–4.81% and 5.13–7.61%, respectively. The major advantage of this method is that MCF derivatization allows conversion of TCE metabolites into their methyl esters in very short time (≤30 s) at room temperature directly in the plasma samples, thus makes it a solventless analysis. The method developed was successfully applied to the plasma samples of humans exposed to TCE.

► Rapid, sensitive and green analytical method for quantitative determination of TCE metabolites in human plasma samples.
► In matrix derivatization of TCE metabolites with MCF directly in plasma samples.
► Reduced derivatization time (30 s) and temperature (25 °C) in comparison to the existing methods.
► Solventless extraction of volatile derivatives by HS-SPME.
► Determination of TCE metabolites in real plasma samples was successfully performed.