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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST003673 |
| Study Title | Identification of plasma metabolites responding to oxycodone exposure in rats |
| Study 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. 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 Name | Kechris |
| First Name | Katerina |
| Address | 13001 E 17th Pl, Aurora, CO 80045 |
| katerina.kechris@cuanschutz.edu | |
| Phone | (303) 724-4363 |
| Submit Date | 2025-01-14 |
| Analysis Type Detail | Other |
| Release Date | 2025-02-05 |
| Release Version | 1 |
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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 source | SAMPLE_DESCRIPTION |
|---|---|---|---|
| SA401741 | UNCO-05152 | EDTA Plasma | baseline blood |
| SA401742 | UNCO-05166 | EDTA Plasma | baseline blood |
| SA401743 | UNCO-05165 | EDTA Plasma | baseline blood |
| SA401744 | UNCO-05164 | EDTA Plasma | baseline blood |
| SA401745 | UNCO-05163 | EDTA Plasma | baseline blood |
| SA401746 | UNCO-05162 | EDTA Plasma | baseline blood |
| SA401747 | UNCO-05161 | EDTA Plasma | baseline blood |
| SA401748 | UNCO-05160 | EDTA Plasma | baseline blood |
| SA401749 | UNCO-05159 | EDTA Plasma | baseline blood |
| SA401750 | UNCO-05158 | EDTA Plasma | baseline blood |
| SA401751 | UNCO-05157 | EDTA Plasma | baseline blood |
| SA401752 | UNCO-05156 | EDTA Plasma | baseline blood |
| SA401753 | UNCO-05155 | EDTA Plasma | baseline blood |
| SA401754 | UNCO-05154 | EDTA Plasma | baseline blood |
| SA401755 | UNCO-05153 | EDTA Plasma | baseline blood |
| SA401756 | UNCO-05151 | EDTA Plasma | baseline blood |
| SA401726 | UNCO-05168 | EDTA Plasma | Intoxication blood |
| SA401727 | UNCO-05182 | EDTA Plasma | Intoxication blood |
| SA401728 | UNCO-05181 | EDTA Plasma | Intoxication blood |
| SA401729 | UNCO-05180 | EDTA Plasma | Intoxication blood |
| SA401730 | UNCO-05179 | EDTA Plasma | Intoxication blood |
| SA401731 | UNCO-05178 | EDTA Plasma | Intoxication blood |
| SA401732 | UNCO-05177 | EDTA Plasma | Intoxication blood |
| SA401733 | UNCO-05176 | EDTA Plasma | Intoxication blood |
| SA401734 | UNCO-05175 | EDTA Plasma | Intoxication blood |
| SA401735 | UNCO-05174 | EDTA Plasma | Intoxication blood |
| SA401736 | UNCO-05173 | EDTA Plasma | Intoxication blood |
| SA401737 | UNCO-05171 | EDTA Plasma | Intoxication blood |
| SA401738 | UNCO-05170 | EDTA Plasma | Intoxication blood |
| SA401739 | UNCO-05169 | EDTA Plasma | Intoxication blood |
| SA401740 | UNCO-05167 | EDTA Plasma | Intoxication 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. |
Combined analysis:
| Analysis ID | AN006031 | AN006032 | AN006033 | AN006034 |
|---|---|---|---|---|
| Analysis type | MS | MS | MS | MS |
| Chromatography type | Reversed phase | Reversed phase | Reversed phase | HILIC |
| Chromatography system | Waters Acquity | Waters Acquity | Waters Acquity | Waters Acquity |
| Column | Waters Acquity BEH C18 (100 x 2mm, 1.7um) | Waters Acquity BEH C18 (100 x 2mm, 1.7um) | Waters Acquity BEH C18 (100 x 2mm, 1.7um) | Waters ACQUITY UPLC BEH Amide (150 x 2.1mm,1.7um) |
| MS Type | Other | Other | Other | Other |
| MS instrument type | Orbitrap | Orbitrap | Orbitrap | Orbitrap |
| MS instrument name | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap |
| Ion Mode | POSITIVE | POSITIVE | NEGATIVE | NEGATIVE |
| Units | relativeMedian of peak area | relativeMedian of peak area | relativeMedian of peak area | relativeMedian of peak area |
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 |
MS:
| MS ID: | MS005742 |
| Analysis ID: | AN006031 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | Other |
| MS Comments: | Metabolon (LC/MS Pos early). These data are normalized across batches to generate the Batch-normalized data and correct for minor instrument technical variation from batch to batch. Essentially, each compound is corrected in instrument batch blocks by registering the medians of each batch to equal one (1.00) and normalizing each data point proportionately (termed the “block correction”). For each metabolite, the raw values in the experimental samples are divided by the median of those samples in each instrument batch, giving each batch and thus the metabolite a median of one. Batch-normalized data simply reflect median-scaled raw data. |
| Ion Mode: | POSITIVE |
| MS ID: | MS005743 |
| Analysis ID: | AN006032 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | Other |
| MS Comments: | Metabolon (LC/MS Pos late). These data are normalized across batches to generate the Batch-normalized data and correct for minor instrument technical variation from batch to batch. Essentially, each compound is corrected in instrument batch blocks by registering the medians of each batch to equal one (1.00) and normalizing each data point proportionately (termed the “block correction”). For each metabolite, the raw values in the experimental samples are divided by the median of those samples in each instrument batch, giving each batch and thus the metabolite a median of one. Batch-normalized data simply reflect median-scaled raw data. |
| Ion Mode: | POSITIVE |
| MS ID: | MS005744 |
| Analysis ID: | AN006033 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | Other |
| MS Comments: | Metabolon (LC/MS Neg). These data are normalized across batches to generate the Batch-normalized data and correct for minor instrument technical variation from batch to batch. Essentially, each compound is corrected in instrument batch blocks by registering the medians of each batch to equal one (1.00) and normalizing each data point proportionately (termed the “block correction”). For each metabolite, the raw values in the experimental samples are divided by the median of those samples in each instrument batch, giving each batch and thus the metabolite a median of one. Batch-normalized data simply reflect median-scaled raw data. |
| Ion Mode: | NEGATIVE |
| MS ID: | MS005745 |
| Analysis ID: | AN006034 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | Other |
| MS Comments: | Metabolon (LC/MS Polar). These data are normalized across batches to generate the Batch-normalized data and correct for minor instrument technical variation from batch to batch. Essentially, each compound is corrected in instrument batch blocks by registering the medians of each batch to equal one (1.00) and normalizing each data point proportionately (termed the “block correction”). For each metabolite, the raw values in the experimental samples are divided by the median of those samples in each instrument batch, giving each batch and thus the metabolite a median of one. Batch-normalized data simply reflect median-scaled raw data. |
| Ion Mode: | NEGATIVE |
