Development of an Analytical Method for Quantitation of 2,2ʹ-Dimorpholinodiethyl Ether (DMDEE) in Rat Plasma, Amniotic Fluid and Fetal Homogenate by UPLC–MS-MS for Determination of Gestational and Lactational Transfer in Rats

Author:

Silinski Melanie A Rehder1,Uenoyama Teruyo1,Fernando Reshan A1,Robinson Veronica G2,Roberts Georgia2,Cunny Helen2,Hubbard Troy2,Waidyanatha Suramya2

Affiliation:

1. Discovery Sciences Unit, RTI International, P.O. Box 12194, Research Triangle Park, NC 27709, USA

2. Division of the National Toxicology Program, NIEHS, P.O. Box 12233, Research Triangle Park, NC 27709, USA

Abstract

Abstract 2,2ʹ-Dimorpholinodiethyl ether (DMDEE) is a specialty amine catalyst used in the production of flexible foams, adhesives and coatings. The potential for occupational exposure to DMDEE is high, but toxicity data are very limited. The objective of this work was to develop a method to quantitate DMDEE in biological matrices to assess gestational and lactational transfer of DMDEE in rats following exposure of dams The method used protein precipitation, followed by removal of phospholipids and analysis of supernatant by ultra-performance liquid chromatography-tandem mass spectrometry. Rat fetuses were homogenized in water prior to protein precipitation and delipidation procedures. The method was evaluated in male Sprague Dawley rat plasma over the concentration range 5 to 1000 ng/mL. The method was linear (r ≥ 0.99), accurate (mean relative error (RE) ≤ ±11.9%) and precise (relative standard deviation (RSD) ≤ 2.7%). The mean absolute recovery was 106%. The limit of detection was 0.262 ng/mL. Standards as high as ∼100,000 ng/mL could be successfully diluted into the calibration range (mean %RE = −14.9; %RSD = 0.5). The method was evaluated in Sprague Dawley rat dam plasma, post-natal day 4 pup plasma, gestational day (GD) 18 amniotic fluid and fetal homogenate (mean %RE ≤ ±11.9; %RSD ≤ 2.3). Concentrations of DMDEE in rat dam plasma, amniotic fluid and fetal homogenate stored for at least 29 days and in pup plasma for at least 18 days at −80°C were within 87.7 to 99.5% of Day 0 concentrations, demonstrating that DMDEE is stable in these matrices. The method was used to quantitate DMDEE in rat plasma, amniotic fluid and fetus samples from a dose range finding toxicology study in which dams were dosed via gavage with DMDEE from GD 6 at doses of 0 (control), 62.5 and 250 mg/kg/day. DMDEE concentration increased with the dose in all matrices examined. The concentration in GD 18 fetuses was almost 2-fold higher than GD 18 dams demonstrating gestational transfer of DMDEE. However, the concentration in post-natal day 4 pup plasma was more than an order of magnitude lower than corresponding dam plasma suggesting less potential for transfer of DMDEE from dams to pups via lactation. There was no significant difference in concentration for male and female pup plasma.

Funder

National Institute of Environmental Health Sciences

Publisher

Oxford University Press (OUP)

Subject

Chemical Health and Safety,Health, Toxicology and Mutagenesis,Toxicology,Environmental Chemistry,Analytical Chemistry

Reference8 articles.

1. JEFFCAT® Catalysts;Huntsman Corporation,2012

2. Chemical Data Reporting (CDR) Database;U.S. Environmental Protection Agency,2016

3. Dimorpholinodiethyl ether;National Toxicology Program, NIH,2006

4. NTP Research Concept: 2,2ʹ-Dimorpholinodiethyl Ether. National Toxicology Program, NIH;Irwin,2008

5. In vitro investigations of a novel wound dressing concept based on biodegradable polyurethane;Rottmar;Science and Technology of Advanced Materials,2015

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