PhD Scientific Days 2024

Budapest, 9-10 July 2024

Pharmaceutical Sciences and Health Technologies I.

Enabling toxicokinetic characterisation of 2,3-epoxypropyl isopropyl ether in the rat by substantial sensitivity improvement of the MS/MS detection


Aliz Széles1, Katalin Monostory2, Tibor Renkecz3
1: Doctoral College Semmelweis University (Hungary); HUN-REN Research Centre for Natural Sciences (Hungary); Toxi-Coop Toxicological Research Centre (Hungary)
2: HUN-REN Research Centre for Natural Sciences (Hungary)
3: Toxi-Coop Toxicological Research Centre (Hungary)

Text of the abstract

2,3-epoxypropyl isopropyl ether is a frequently used material during epoxy resin manufacturing process. There is still little known about the attainable systemic concentration of such chemicals in laboratory animals and in the human body. Present work can provide valuable information to assist exposure assessment/biomonitoring in occupational safety studies.
The LC-MS/MS method used gradient elution [mobile phase A (0.5% formic acid in ultrapure water) B (0.5% formic acid in acetonitrile)] on a YMC-Triart C18 column. As internal standard tert-butyl glycidyl ether was used since no stable isotope labelled analogue of the analyte was available. The Shimadzu LCMS-8060 triple quadrupole tandem mass spectrometer was operated in MRM mode with APCI ion source and the ethylnitrilium adduct form of the precursor ion was selected for fragmentation. The LLOQ for the analyte was 0.01 µg/mL over a 0.01–10 µg/mL range. The rat plasma matrix did not cause any signal suppression. The mean recovery was 106 % and 94.6 % at high (8 µg/mL) and low (0.03 µg/mL) level of concentration. The plasma samples proved to be stable at 75C ± 10C for at least 26 days and can be subjected to 3 freeze-thaw cycles and for at least 4 hour-storage on benchtop at room temperature.
In a toxicokinetic (TK) study, a single dose (1000 mg/kg; 1500 mg/kg and 2000 mg/kg) of 2,3-epoxypropyl isopropyl ether was administered orally to rats and TK plasma sparse sampling was performed at 9 time-points. The TK evaluation results with the method performance characterization will be presented in details.