Summary of Study ST003673

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002278. The data can be accessed directly via it's Project DOI: 10.21228/M85N81 This work is supported by NIH grant, U2C- DK119886.

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Study IDST003673
Study TitleIdentification of plasma metabolites responding to oxycodone exposure in rats
Study SummaryMetabolomics studies of prescription opioid medications including oxycodone can provide insights into biochemical mechanisms of the addiction cycle and prognosis prediction. Although oxycodone has an elevated abuse liability profile compared to other opioids, many human and rodent metabolomics studies have not been specifically focused on oxycodone. In this study, we investigated metabolomics changes associated with oxycodone exposure using plasma samples from 16 rats at pre-exposure and intoxication time points. Among the 798 metabolites with low levels of missingness, 364 showed significant changes be-tween pre-exposure and intoxication (FDR < 0.01) including succinate, oleamide, and sarcosine. We identified four pathways including tryptophan metabolism that were nominally enriched among the metabolites that change with oxycodone exposure (p < 0.05). Furthermore, we identified sev-eral metabolites that showed nominal correlations with the Addiction Index (composite of ox-ycodone behaviors), 17 at pre-exposure and 8 at intoxication.
Institute
University of Colorado Anschutz Medical Campus
Last NameKechris
First NameKaterina
Address13001 E 17th Pl, Aurora, CO 80045
Emailkaterina.kechris@cuanschutz.edu
Phone(303) 724-4363
Submit Date2025-01-14
Analysis Type DetailOther
Release Date2025-02-05
Release Version1
Katerina Kechris Katerina Kechris
https://dx.doi.org/10.21228/M85N81
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR002278
Project DOI:doi: 10.21228/M85N81
Project Title:Identification of plasma metabolites responding to oxycodone exposure in rats.
Project Summary:Metabolomics studies of prescription opioid medications including oxycodone can provide insights into biochemical mechanisms of the addiction cycle and prognosis prediction. Although oxycodone has an elevated abuse liability profile compared to other opioids, many human and rodent metabolomics studies have not been specifically focused on oxycodone. In this study, we investigated metabolomics changes associated with oxycodone exposure using plasma samples from 16 rats at pre-exposure and intoxication time points.
Institute:University of Colorado Anschutz Medical Campus
Department:Biostatistics and Informatics
Laboratory:KechrisLab
Last Name:Kechris
First Name:Katerina
Address:13001 E 17th Pl, Aurora, CO 80045
Email:katerina.kechris@cuanschutz.edu
Phone:(303)724-4363
Funding Source:DA044451

Subject:

Subject ID:SU003805
Subject Type:Other organism
Subject Species:Rattus norvegicus
Taxonomy ID:10116

Factors:

Subject type: Other organism; Subject species: Rattus norvegicus (Factor headings shown in green)

mb_sample_id local_sample_id SAMPLE_DESCRIPTION
SA401741UNCO-05152baseline blood
SA401742UNCO-05166baseline blood
SA401743UNCO-05165baseline blood
SA401744UNCO-05164baseline blood
SA401745UNCO-05163baseline blood
SA401746UNCO-05162baseline blood
SA401747UNCO-05161baseline blood
SA401748UNCO-05160baseline blood
SA401749UNCO-05159baseline blood
SA401750UNCO-05158baseline blood
SA401751UNCO-05157baseline blood
SA401752UNCO-05156baseline blood
SA401753UNCO-05155baseline blood
SA401754UNCO-05154baseline blood
SA401755UNCO-05153baseline blood
SA401756UNCO-05151baseline blood
SA401726UNCO-05168Intoxication blood
SA401727UNCO-05182Intoxication blood
SA401728UNCO-05181Intoxication blood
SA401729UNCO-05180Intoxication blood
SA401730UNCO-05179Intoxication blood
SA401731UNCO-05178Intoxication blood
SA401732UNCO-05177Intoxication blood
SA401733UNCO-05176Intoxication blood
SA401734UNCO-05175Intoxication blood
SA401735UNCO-05174Intoxication blood
SA401736UNCO-05173Intoxication blood
SA401737UNCO-05171Intoxication blood
SA401738UNCO-05170Intoxication blood
SA401739UNCO-05169Intoxication blood
SA401740UNCO-05167Intoxication blood
Showing results 1 to 31 of 31

Collection:

Collection ID:CO003798
Collection Summary:For this study, the Oxycodone Biobank20 provided 32 plasma samples from 16 rats (8 females and 8 males; 2 samples per rat) at pre-exposure and intoxication time points. While the rats were anesthetized for the intravenous catheter surgery, 200- to 400-μl blood (pre-exposure) was collected through retroorbital bleed in EDTA-coated (Ethylene Diamine Tetra Acetic acid)tubes that were immediately inverted five times. Blood samples were processed within 1 hour of collection by centrifugation at 2000 x g at room temperature (RT) for 10 minutes to pellet the erythrocytes. The supernatant plasma was immediately transferred into a fresh tube, scored for quality on a scale from 0 to 5, snap-frozen on dry ice, and stored at –80°C. Samples were shipped on dry ice overnight to the Metabolon facility in North Carolina for metabolite characterization.
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR003814
Treatment Summary:For this study, the Oxycodone Biobank provided 32 plasma samples from 16 rats (8 females and 8 males; 2 samples per rat) at pre-exposure and intoxication time points. While the rats were anesthetized for the intravenous catheter surgery, 200- to 400-μl blood (pre-exposure) was collected through retroorbital bleed in EDTA-coated tubes that were immediately inverted five times. Oxycodone (Sigma-Aldrich) was dissolved in 0.9% sterile saline (Hospira) and administered at 150 mg/kg per infusion intravenously. This dose of oxycodone per infusion was selected based on previous studies and because it produces significant plasma oxycodone concentrations (40 ng/ml). Rats were familiarized and trained to self-administer during short access (ShA) and long access (LgA). There were 4 ShA sessions of 2 h and 14 LgA session of 12 h.

Sample Preparation:

Sampleprep ID:SP003812
Sampleprep Summary:Blood samples were processed within 1 hour of collection by centrifugation at 2000 x g at room temperature (RT) for 10 minutes to pellet the erythrocytes. The supernatant plasma was immediately transferred into a fresh tube, scored for quality on a scale from 0 to 5, snap-frozen on dry ice, and stored at –80°C. Samples were shipped on dry ice overnight to the Metabolon facility in North Carolina for metabolite characterization. Samples were divided into five fractions: 2 for analysis by two separate reverse phase (RP)/UPLC-MS/MS methods with positive ion mode electrospray ionization (ESI), 1 for analysis by RP/UPLC-MS/MS with negative ion mode ESI, 1 for analysis by hydrophilic interaction chromatophaphy (HILIC)/UPLC-MS/MS with negative ion mode ESI, and 1 sample was reserved for backup.

Chromatography:

Chromatography ID:CH004583
Chromatography Summary:Low pH polar (LC/MS Pos early)
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH C18 (100 x 2mm, 1.7um)
Column Temperature:40-50
Flow Gradient:Linear gradient from 5% B to 80% B over 3.35 minutes
Flow Rate:0.35 mL/min
Solvent A:100% water; 0.1% formic acid; 0.05% PFPA, pH ~2.5
Solvent B:100% methanol; 0.1% formic acid; 0.05% PFPA, pH ~2.5
Chromatography Type:Reversed phase
  
Chromatography ID:CH004584
Chromatography Summary:Low pH Lipophilic (LC/MS Pos late)
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH C18 (100 x 2mm, 1.7um)
Column Temperature:40-50
Flow Gradient:Linear gradient from 40% B to 99.5% B over 1.0 minute, hold 99.5% B for 2.4 minutes.
Flow Rate:0.60 mL/min
Solvent A:100% water; 0.1% formic acid; 0.05% PFPA, pH ~2.5
Solvent B:50% methanol/50% acetonitrile; 0.1% formic acid; 0.05% PFPA, pH ~2.5
Chromatography Type:Reversed phase
  
Chromatography ID:CH004585
Chromatography Summary:High pH (LC/MS Neg)
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH C18 (100 x 2mm, 1.7um)
Column Temperature:40-50
Flow Gradient:Linear gradient from 0.5 to 70% B over 4.0 minutes, then rapid gradient to 99% B in 0.5 minutes.
Flow Rate:0.35 mL/min
Solvent A:100% water; 6.5 mM ammonium bicarbonate, pH 8
Solvent B:95% methanol/5% water; 6.5 mM ammonium bicarbonate
Chromatography Type:Reversed phase
  
Chromatography ID:CH004586
Chromatography Summary:HILIC (LC/MS Polar Neg)
Instrument Name:Waters Acquity
Column Name:Waters ACQUITY UPLC BEH Amide (150 x 2.1mm,1.7um)
Column Temperature:40-50
Flow Gradient:Linear gradient from 5% B to 50% B in 3.5 minutes, then linear gradient from 50% B to 95% B in 2 minutes.
Flow Rate:0.50 mL/min
Solvent A:15% water/5% methanol/80% acetonitrile; 10 mM ammonium formate, (effective pH 10.16 with NH4OH)
Solvent B:50% water/50% acetonitrile; 10 mM ammonium formate, (effective pH 10.60 with NH4OH)
Chromatography Type:HILIC

Analysis:

Analysis ID:AN006031
Analysis Type:MS
Chromatography ID:CH004583
Num Factors:2
Num Metabolites:225
Units:relativeMedian of peak area
  
Analysis ID:AN006032
Analysis Type:MS
Chromatography ID:CH004584
Num Factors:2
Num Metabolites:218
Units:relativeMedian of peak area
  
Analysis ID:AN006033
Analysis Type:MS
Chromatography ID:CH004585
Num Factors:2
Num Metabolites:391
Units:relativeMedian of peak area
  
Analysis ID:AN006034
Analysis Type:MS
Chromatography ID:CH004586
Num Factors:2
Num Metabolites:107
Units:relativeMedian of peak area
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