| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Paraxanthine-d6 has no independent pharmacological target as a stable isotope internal standard. The unlabeled paraxanthine is an active metabolite of caffeine and an adenosine A1 and A2 receptor antagonist with Ki values of 35 uM and 22 uM, respectively. In vivo, paraxanthine increases striatal cGMP and extracellular striatal dopamine levels and locomotor activity, promotes wakefulness, and increases core temperature. It also inhibits adenosine receptor agonist-induced motor depression and lacks the behavioral anxiety effects of caffeine.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
As a stable isotope internal standard, Paraxanthine-d6 is not tested for in vitro pharmacological activity. It is added to biological samples to enable accurate quantification of endogenous paraxanthine by LC-MS/MS or GC-MS. The deuterium labeling provides a distinct mass shift, allowing correction for matrix effects, extraction recovery, and instrument variability. Paraxanthine-d6 is used in caffeine metabolism studies to quantify paraxanthine as a measure of CYP1A2 activity. |
| ln Vivo |
Paraxanthine-d6 has no in vivo pharmacological activity as a therapeutic agent. It is used as an internal standard for quantifying paraxanthine in biological samples obtained from animal and human studies, including plasma, urine, and tissue homogenates. Paraxanthine is an important biomarker for caffeine metabolism and CYP1A2 activity, and the deuterated standard enables accurate measurement of this metabolite in pharmacokinetic, metabolism, and pharmacogenetic studies. Paraxanthine itself is pharmacologically active as an adenosine receptor antagonist.
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| Enzyme Assay |
For in vitro LC-MS/MS quantification, Paraxanthine-d6 is dissolved in an appropriate solvent (methanol, DMSO, or 0.1% formic acid) to prepare a stock solution (e.g., 1 mg/mL). The internal standard is added to biological samples (plasma, serum, urine, cell lysates, or microsomal incubation mixtures) at a fixed concentration (e.g., 10-500 ng/mL). For plasma samples, protein precipitation is performed by adding 3-5 volumes of methanol or acetonitrile containing the internal standard, followed by vortexing and centrifugation (10,000-15,000 rpm, 10 minutes). The supernatant is transferred and evaporated to dryness under nitrogen or directly analyzed by LC-MS/MS. Paraxanthine-d6 can also be used for GC-MS analysis after derivatization. The paraxanthine/paraxanthine-d6 peak area ratio is used for quantification, correcting for matrix effects and extraction recovery.
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| Cell Assay |
For cell-based studies, cells expressing CYP1A2 (e.g., primary hepatocytes, HepG2 cells, or CYP1A2-transfected cells) are cultured in standard medium (DMEM or Williams' E medium with 10% FBS). Cells are treated with caffeine (0.1-1 mM) to generate paraxanthine via CYP1A2-mediated N3-demethylation. After incubation for 0-24 hours, cell culture supernatants or cell lysates are collected. Paraxanthine-d6 is added to samples as an internal standard at a fixed concentration (e.g., 10-100 ng/mL). Following protein precipitation with methanol or acetonitrile and centrifugation, samples are analyzed by LC-MS/MS to quantify paraxanthine formation as a measure of CYP1A2 enzyme activity. For time-course studies, the internal standard is added to all samples at a consistent concentration to correct for sample handling and instrument variability.
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| Animal Protocol |
For in vivo pharmacokinetic or metabolism studies, Paraxanthine-d6 is not administered to animals independently. It is used as an internal standard for quantifying paraxanthine in biological samples obtained from animals treated with caffeine or test compounds affecting CYP1A2 activity. After collection of plasma (via tail vein or cardiac puncture), urine, or tissue homogenates (liver, brain), the internal standard is added at a fixed concentration (e.g., 10-500 ng/mL). Samples are processed by protein precipitation with methanol or acetonitrile, followed by centrifugation and LC-MS/MS analysis. For clinical studies, Paraxanthine-d6 is similarly added to patient plasma or urine samples to quantify paraxanthine as a measure of caffeine metabolism and CYP1A2 phenotype.
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| ADME/Pharmacokinetics |
Paraxanthine-d6 is an internal standard and does not have independent pharmacokinetic parameters. Paraxanthine is an active caffeine metabolite with a plasma half-life of approximately 3-5 hours in humans (longer than caffeine's 2-5 hour half-life). It is eliminated primarily by renal excretion (60-70% unchanged) and further metabolism to xanthine derivatives via demethylation. The volume of distribution is approximately 0.5-0.6 L/kg, and plasma protein binding is about 40%. The deuterated version is used to calibrate analytical methods.
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| Toxicity/Toxicokinetics |
Paraxanthine has a similar toxicity profile to caffeine. In mice, the LD50 of paraxanthine is approximately 350 mg/kg (intraperitoneal) and 800 mg/kg (oral). At high doses, it can cause CNS stimulation, tachycardia, anxiety, insomnia, and gastrointestinal distress. The deuterated version is chemically identical except for isotopic substitution and exhibits the same safety profile. Standard laboratory safety precautions for handling xanthine derivatives apply. Not intended for human consumption.
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| References |
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| Additional Infomation |
Paraxanthine-d6 is not a drug but a deuterium-labeled stable isotope internal standard. It has no approved therapeutic status, no clinical trial history as a therapeutic agent, and is not intended for human consumption. This compound is used for research applications including as an internal standard for GC-MS or LC-MS quantification of paraxanthine, caffeine metabolic studies (particularly CYP1A2 phenotyping), adenosine receptor antagonist research, and clinical biomarker studies for caffeine metabolism and drug-drug interactions. Paraxanthine-d6 is an important tool for studying paraxanthine's role in CNS function, sleep/wake regulation, and locomotor activity without the confounding effects of caffeine. Available with ≥99% deuterated purity (d1-d6, ≤1% d0).
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| Molecular Formula |
C7H2D6N4O2
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|---|---|
| Molecular Weight |
186.20
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| Exact Mass |
186.102
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| CAS # |
117490-41-2
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| Related CAS # |
Paraxanthine;611-59-6
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| PubChem CID |
53442229
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| Appearance |
White to off-white solid powder
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| LogP |
-0.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
13
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| Complexity |
267
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])([2H])N1C=NC2=C1C(=O)N(C(=O)N2)C([2H])([2H])[2H]
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| InChi Key |
QUNWUDVFRNGTCO-WFGJKAKNSA-N
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| InChi Code |
InChI=1S/C7H8N4O2/c1-10-3-8-5-4(10)6(12)11(2)7(13)9-5/h3H,1-2H3,(H,9,13)/i1D3,2D3
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| Chemical Name |
1,7-bis(trideuteriomethyl)-3H-purine-2,6-dione
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~10 mg/mL (~53.7 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (5.37 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (10.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (5.37 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (10.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 1 mg/mL (5.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (10.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.3706 mL | 26.8528 mL | 53.7057 mL | |
| 5 mM | 1.0741 mL | 5.3706 mL | 10.7411 mL | |
| 10 mM | 0.5371 mL | 2.6853 mL | 5.3706 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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