PMID- 33031531
OWN - NLM
STAT- MEDLINE
DCOM- 20211111
LR  - 20211112
IS  - 1945-2403 (Electronic)
IS  - 0146-4760 (Print)
IS  - 0146-4760 (Linking)
VI  - 45
IP  - 9
DP  - 2021 Nov 9
TI  - Development of an Analytical Method for Quantitation of 2,2'-Dimorpholinodiethyl 
      Ether (DMDEE) in Rat Plasma, Amniotic Fluid and Fetal Homogenate by UPLC-MS-MS 
      for Determination of Gestational and Lactational Transfer in Rats.
PG  - 1036-1041
LID - 10.1093/jat/bkaa158 [doi]
AB  - 2,2'-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  approximately 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 degrees 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.
CI  - (c) The Author(s) 2020. Published by Oxford University Press. All rights reserved. 
      For permissions, please e-mail: journals.permissions@oup.com.
FAU - Silinski, Melanie A Rehder
AU  - Silinski MAR
AD  - Discovery Sciences Unit, RTI International, P.O. Box 12194, Research Triangle 
      Park, NC 27709, USA.
FAU - Uenoyama, Teruyo
AU  - Uenoyama T
AD  - Discovery Sciences Unit, RTI International, P.O. Box 12194, Research Triangle 
      Park, NC 27709, USA.
FAU - Fernando, Reshan A
AU  - Fernando RA
AD  - Discovery Sciences Unit, RTI International, P.O. Box 12194, Research Triangle 
      Park, NC 27709, USA.
FAU - Robinson, Veronica G
AU  - Robinson VG
AD  - Division of the National Toxicology Program, NIEHS, P.O. Box 12233, Research 
      Triangle Park, NC 27709, USA.
FAU - Roberts, Georgia
AU  - Roberts G
AD  - Division of the National Toxicology Program, NIEHS, P.O. Box 12233, Research 
      Triangle Park, NC 27709, USA.
FAU - Cunny, Helen
AU  - Cunny H
AD  - Division of the National Toxicology Program, NIEHS, P.O. Box 12233, Research 
      Triangle Park, NC 27709, USA.
FAU - Hubbard, Troy
AU  - Hubbard T
AD  - Division of the National Toxicology Program, NIEHS, P.O. Box 12233, Research 
      Triangle Park, NC 27709, USA.
FAU - Waidyanatha, Suramya
AU  - Waidyanatha S
AD  - Division of the National Toxicology Program, NIEHS, P.O. Box 12233, Research 
      Triangle Park, NC 27709, USA.
LA  - eng
GR  - HHSN273201400022C/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PL  - England
TA  - J Anal Toxicol
JT  - Journal of analytical toxicology
JID - 7705085
RN  - 0 (Ethers)
RN  - 0F5N573A2Y (Ether)
SB  - IM
MH  - *Amniotic Fluid
MH  - Animals
MH  - Chromatography, High Pressure Liquid
MH  - Chromatography, Liquid
MH  - Ether
MH  - Ethers
MH  - Female
MH  - Lactation
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Tandem Mass Spectrometry
PMC - PMC8577537
EDAT- 2020/10/09 06:00
MHDA- 2021/11/12 06:00
PMCR- 2021/10/08
CRDT- 2020/10/08 17:14
PHST- 2020/01/28 00:00 [received]
PHST- 2020/09/16 00:00 [revised]
PHST- 2020/10/07 00:00 [accepted]
PHST- 2020/10/09 06:00 [pubmed]
PHST- 2021/11/12 06:00 [medline]
PHST- 2020/10/08 17:14 [entrez]
PHST- 2021/10/08 00:00 [pmc-release]
AID - 5919705 [pii]
AID - bkaa158 [pii]
AID - 10.1093/jat/bkaa158 [doi]
PST - ppublish
SO  - J Anal Toxicol. 2021 Nov 9;45(9):1036-1041. doi: 10.1093/jat/bkaa158.