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. 2013 Sep 16;18(9):11452-66.
doi: 10.3390/molecules180911452.

Determination and pharmacokinetics of di-(2-ethylhexyl) phthalate in rats by ultra performance liquid chromatography with tandem mass spectrometry

Wan-Ling Chang-Liao  1 , Mei-Ling Hou, Li-Wen Chang, Chia-Jung Lee, Yin-Meng Tsai, Lie-Chwen Lin, Tung-Hu Tsai
Affiliations

Determination and pharmacokinetics of di-(2-ethylhexyl) phthalate in rats by ultra performance liquid chromatography with tandem mass spectrometry

Wan-Ling Chang-Liao et al. Molecules. .

Abstract

Di-(2-ethylhexyl) phthalate (DEHP) is used to increase the flexibility of plastics for industrial products. However, the illegal use of the plasticizer DEHP in food and drinks has been reported in Taiwan in 2011. In order to assess the exact extent of the absorption of DEHP via the oral route, the aim of this study is to develop a reliable and validated ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method to evaluate the oral bioavailability of DEHP in rats. The optimal chromatographic separation of DEHP and butyl benzyl phthalate (BBP; used as internal standard) were achieved on a C₁₈ column. The mobile phase was consisted of 5 mM ammonium acetate-methanol (11:89, v/v) with a flow rate of 0.25 mL/min. The monitoring ion transitions were m/z 391.4 → 149.0 for DEHP and m/z 313.3 → 149.0 for BBP. The mean matrix effects of DEHP at low, medium and high concentrations were 94.5 ± 5.7% and 100.1 ± 2.3% in plasma and feces homogenate samples, respectively. In conclusion, the validated UPLC-MS/MS method is suitable for analyzing the rat plasma sample of DEHP and the oral bioavailability of DEHP was about 7% in rats.

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Figures

Figure 1
Figure 1
Representative product ion mass spectra and chemical structures of (A) DEHP and (B) BBP (internal standard).
Figure 2
Figure 2
Representative UPLC-MS/MS chromatograms for the analytes. (A) Blank plasma sample; (B) blank plasma sample spiked with 0.5 μg/mL DEHP standard, and (C) plasma sample collected from rat plasma after administration of DEHP (10 mg/kg, i.v.). (D) Blank fecal sample; (E) blank fecal sample spiked with 1 μg/mL DEHP standard, and (F) fecal sample (400-fold dilution) collected from rat feces after administration of DEHP (100 mg/kg, p.o.) at 0–12 h. 1. Internal standard (BBP 1 μg/mL); 2. DEHP.
Figure 3
Figure 3
Concentration-time profile of DEHP after drug administration (10 mg/kg, i.v.; 100 mg/kg, p.o.) in rat plasma. Data are presented as mean ± S.E.M. (n = 6).
Figure 4
Figure 4
Fecal excretion profile of DEHP following a single oral administration of DEHP (100 mg/kg); results are expressed as mean ± S.E.M. (n = 6).
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