| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
Cyclooxygenase-3 (COX-3). Phenacetin-d5 is a selective COX-3 inhibitor, similarly to its non-labeled parent compound. Phenacetin is known to inhibit the COX enzyme, blocking the conversion of arachidonic acid to prostaglandins, which are mediators of pain and fever. Additionally, phenacetin is a well-established probe substrate for CYP1A2, an important drug-metabolizing enzyme.
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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].
In vitro, phenacetin-d5 is used primarily as an internal standard for the quantitation of phenacetin. Its parent compound, phenacetin, is a selective COX-3 inhibitor and also a probe substrate of cytochrome P450 1A2 in human liver microsomes, where it is metabolized to acetaminophen. Phenacetin produces analgesia and antipyresis via COX-3 inhibition in the central nervous system. |
| ln Vivo |
In vivo, phenacetin is absorbed well after oral administration, producing analgesic and antipyretic effects by inhibiting prostaglandin synthesis. The non-deuterated phenacetin is metabolized by CYP1A2 to acetaminophen (paracetamol), which is further conjugated and excreted. Phenacetin-d5, when used as a tracer, follows the same metabolic fate, allowing for precise PK studies without altering the drug's pharmacological properties.
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| Enzyme Assay |
A direct binding ELISA or enzyme activity assay is not typically used for phenacetin-d5. Instead, its identity and purity are confirmed by NMR and LC-MS. For use as a CYP1A2 probe, a metabolic assay is performed: human liver microsomes are incubated with phenacetin (or phenacetin-d5 as an internal standard) and NADPH, and the production of acetaminophen is measured by LC-MS/MS. The kinetic parameters (Km, Vmax) for O-deethylation are calculated.
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| Cell Assay |
For in vitro cellular assays, human primary hepatocytes or HepG2 cells expressing CYP1A2 are cultured. Cells are treated with phenacetin (0.1-1000 uM) for 1-4 hours to measure CYP1A2 activity. Acetaminophen production in the culture medium is quantified by LC-MS/MS. Cytotoxicity is assessed using an LDH release assay. For internal standard use, phenacetin-d5 is added at a fixed concentration to samples (e.g., plasma, urine, tissue homogenates) before LC-MS/MS analysis to correct for matrix effects and instrument variability.
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| Animal Protocol |
No in vivo animal studies are performed for phenacetin-d5 alone as it is an analytical standard. For pharmacokinetic studies using phenacetin as a CYP1A2 probe, rats are administered phenacetin orally (e.g., 10-50 mg/kg). Blood samples are collected at multiple time points. Phenacetin-d5 is added to each sample as an internal standard before LC-MS/MS analysis to quantify the remaining phenacetin and its metabolite acetaminophen. Pharmacokinetic parameters (Cmax, Tmax, t1/2, AUC, clearance) are calculated for parent and metabolite.
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| ADME/Pharmacokinetics |
Phenacetin-d5 has a molecular weight of 184.25 g/mol and a formula of C10H8D5NO2. It is the deuterated analog of phenacetin, with identical chemical and physical properties except for the substitution of hydrogen with deuterium. It is used as an internal standard for LC-MS/MS quantification. Solubility in DMSO is 100 mg/mL (542.74 mM). The non-deuterated phenacetin is well-absorbed orally, highly plasma protein-bound, and has a half-life of 1-2 hours.
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| Toxicity/Toxicokinetics |
Phenacetin is reasonably anticipated to be a human carcinogen, and analgesic mixtures containing phenacetin are listed as known human carcinogens. Phenacetin can cause nephrotoxicity (analgesic nephropathy) with long-term use and is hepatotoxic. Phenacetin-d5, due to structural similarity, should be handled as a potential carcinogen. The parent drug has been banned or withdrawn in many countries due to safety concerns. Standard precautions for handling potentially carcinogenic substances apply.
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| References |
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| Additional Infomation |
Phenacetin-d5 is a research-grade stable isotope-labeled compound not approved for clinical use. It is intended for use as an internal standard in LC-MS/MS quantification of phenacetin in biological matrices for drug metabolism, pharmacokinetic, and bioequivalence studies. Phenacetin is a selective COX-3 inhibitor and a CYP1A2 probe substrate. This product is for laboratory research only and is not for human therapeutic use.
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| Molecular Formula |
C10H13NO2
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| Molecular Weight |
179.21572
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| Exact Mass |
184.126
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| CAS # |
69323-74-6
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| Related CAS # |
Phenacetin;62-44-2
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| PubChem CID |
12274536
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| Appearance |
White to off-white solid powder
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| LogP |
1.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
13
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| Complexity |
162
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCOC1=CC=C(C=C1)NC(=O)C
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| InChi Key |
CPJSUEIXXCENMM-WNWXXORZSA-N
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| InChi Code |
InChI=1S/C10H13NO2/c1-3-13-10-6-4-9(5-7-10)11-8(2)12/h4-7H,3H2,1-2H3,(H,11,12)/i1D3,3D2
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| Chemical Name |
N-[4-(1,1,2,2,2-pentadeuterioethoxy)phenyl]acetamide
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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: 100 mg/mL (542.74 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.5797 mL | 27.8987 mL | 55.7973 mL | |
| 5 mM | 1.1159 mL | 5.5797 mL | 11.1595 mL | |
| 10 mM | 0.5580 mL | 2.7899 mL | 5.5797 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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