Gas chromatography/mass spectrometry measurement of xenon in gas-loaded liposomes for neuroprotective applications.
BACKGROUND
We have produced a liposomal formulation of xenon (Xe-ELIP) as a neuroprotectant for inhibition of brain damage in stroke patients. This mandates development of a reliable assay to measure the amount of dissolved xenon released from Xe-ELIP in water and blood samples.


METHODS
Gas chromatography/mass spectrometry (GC/MS) was used to quantify xenon gas released into the headspace of vials containing Xe-ELIP samples in water or blood. In order to determine blood concentration of xenon in vivo after Xe-ELIP administration, 6 mg of Xe-ELIP lipid was infused intravenously into rats. Blood samples were drawn directly from a catheterized right carotid artery. After introduction of the samples, each vial was allowed to equilibrate to 37°C in a water bath, followed by 20 minutes of sonication prior to headspace sampling. Xenon concentrations were calculated from a gas dose-response curve and normalized using the published xenon water-gas solubility coefficient.


RESULTS
The mean corrected percent of xenon from Xe-ELIP released into water was 3.87 ± 0.56% (SD, n = 8), corresponding to 19.3 ± 2.8 μL/mg lipid, which is consistent with previous independent Xe-ELIP measurements. The corresponding xenon content of Xe-ELIP in rat blood was 23.38 ± 7.36 μL/mg lipid (n = 8). Mean rat blood xenon concentration after intravenous administration of Xe-ELIP was 14 ± 10 μM, which is approximately 15% of the estimated neuroprotective level.


CONCLUSIONS
Using this approach, we have established a reproducible method for measuring dissolved xenon in fluids. These measurements have established that neuroprotective effects can be elicited by less than 20% of the calculated neuroprotective xenon blood concentration. More work will have to be done to establish the protective xenon pharmacokinetic range. Copyright © 2016 John Wiley & Sons, Ltd.
Department of Internal Medicine, Division of Cardiovascular Medicine, University of Texas Health Science Center - Houston, 1941 East Road, Houston, TX, 77054, USA.
Melvin E
http://orcid.org/0000-0001-7458-0659
ME
Klegerman
Department of Internal Medicine, Division of Cardiovascular Medicine, University of Texas Health Science Center - Houston, 1941 East Road, Houston, TX, 77054, USA.
Melanie R
MR
Moody
Department of Internal Medicine, Division of Cardiovascular Medicine, University of Texas Health Science Center - Houston, 1941 East Road, Houston, TX, 77054, USA.
Jermaine R
JR
Hurling
Department of Internal Medicine, Division of Cardiovascular Medicine, University of Texas Health Science Center - Houston, 1941 East Road, Houston, TX, 77054, USA.
Tao
T
Peng
Department of Internal Medicine, Division of Cardiovascular Medicine, University of Texas Health Science Center - Houston, 1941 East Road, Houston, TX, 77054, USA.
Shao-Ling
SL
Huang
Department of Internal Medicine, Division of Cardiovascular Medicine, University of Texas Health Science Center - Houston, 1941 East Road, Houston, TX, 77054, USA.
David D
DD
McPherson
D000818:Animals; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D057230:Limit of Detection; D016014:Linear Models; D008081:Liposomes / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D018696:Neuroprotective Agents / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D014978:Xenon / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics
D008081:Liposomes; D018696:Neuroprotective Agents; D014978:Xenon
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