| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
4-Hydroxymephenytoin-d3 has no direct pharmacological target as an internal standard. However, its parent, 4-Hydroxymephenytoin, is the primary metabolite used to phenotype CYP2C19 enzyme activity. The unlabeled 4-Hydroxymephenytoin is used to measure the rate of a specific metabolic reaction, making the enzyme CYP2C19 its indirect target. This enzyme is responsible for the metabolism of many clinically important drugs, including proton pump inhibitors and antidepressants.
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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].
The in vitro activity of 4-Hydroxymephenytoin-d3 is not measured directly. Instead, the unlabeled 4-Hydroxymephenytoin is used as a standard. Its rate of formation from its parent drug, mephenytoin, is a measure of CYP2C19 enzyme activity. This activity is used in phenotyping studies to determine if an individual is a poor, intermediate, extensive, or ultrarapid metabolizer of CYP2C19 substrates. This has significant implications for drug efficacy and safety. |
| ln Vivo |
In vivo, 4-Hydroxymephenytoin is produced from mephenytoin by the action of the CYP2C19 enzyme. Its urinary concentration is used to calculate a metabolic ratio, which reflects the activity of this enzyme in the liver. This is the basis for the "mephenytoin test" used in clinical and research settings to determine an individual's CYP2C19 genotype and phenotype, influencing drug choice and dosage. The deuterated form is used as a standard to measure this accurately.
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| Enzyme Assay |
4-Hydroxymephenytoin-d3 is used as an internal standard for in vitro assays. To set up a CYP2C19 phenotyping assay, a stock solution is prepared by dissolving the compound in an appropriate solvent like methanol. A fixed, known amount of this standard is spiked into biological samples (e.g., plasma, urine, or microsomal incubations) before any sample processing steps. This corrects for any loss of the analyte during extraction and provides a precise ratio for quantification by LC-MS or GC-MS.
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| Cell Assay |
For in vitro cellular experiments, 4-Hydroxymephenytoin-d3 is not used as a treatment. Instead, it serves as an analytical standard. Primary human hepatocytes or liver microsomes are incubated with the parent drug, mephenytoin. After a defined period, the reaction is stopped, and a fixed amount of 4-Hydroxymephenytoin-d3 is added to the sample. The sample is then processed and analyzed by LC-MS to measure the amount of 4-Hydroxymephenytoin formed, which is a direct measure of CYP2C19 metabolic activity in that sample.
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| Animal Protocol |
4-Hydroxymephenytoin-d3 is not administered to animals directly for efficacy studies. It is used as an analytical standard to measure the formation of the unlabeled metabolite in samples from animal studies. For example, in a toxicology study, rats or mice are administered mephenytoin. Urine or plasma samples are collected. The deuterated internal standard is added to these samples, and the concentration of 4-Hydroxymephenytoin is determined by LC-MS. The ratio of metabolite to parent drug in the urine provides the metabolic ratio used to assess CYP2C19 activity.
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| ADME/Pharmacokinetics |
4-Hydroxymephenytoin-d3 is a stable isotope-labeled compound and does not have its own pharmacokinetic parameters separate from the unlabeled metabolite. The unlabeled 4-Hydroxymephenytoin is a phase I metabolite that is further metabolized (e.g., via glucuronidation) and is excreted in urine. Its appearance in plasma and urine is a direct reflection of the clearance of mephenytoin and the activity of CYP2C19. Its half-life in the body is short (hours).
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| Toxicity/Toxicokinetics |
4-Hydroxymephenytoin is a well-studied metabolite with low toxicity at the levels encountered in research. The labeled compound, 4-Hydroxymephenytoin-d3, is chemically similar and is used in very small, non-toxic quantities (micrograms to milligrams). Standard laboratory safety precautions for handling organic chemicals, including the use of gloves and eye protection, are sufficient.
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| References |
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| Additional Infomation |
4-Hydroxymephenytoin-d3 is not a drug but a stable isotope-labeled internal standard. It is used for the accurate quantification of mephenytoin 4-hydroxylase (CYP2C19) activity. This is a critical tool for clinical research, pharmaceutical development, and personalized medicine. It is used to study genetic polymorphisms in drug metabolism and to evaluate potential drug-drug interactions, as many drugs inhibit or induce this important enzyme.
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| Molecular Formula |
C12H11D3N2O3
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|---|---|
| Molecular Weight |
237.27
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| Exact Mass |
237.119
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| CAS # |
1173022-56-4
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| Related CAS # |
4-Hydroxymephenytoin;61837-65-8
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| PubChem CID |
45039459
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| Appearance |
White to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.568
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| LogP |
0.66
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
17
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| Complexity |
337
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])([2H])N1C(=O)C(NC1=O)(CC)C2=CC=C(C=C2)O
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| InChi Key |
OQPLORUDZLXXPD-BMSJAHLVSA-N
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| InChi Code |
InChI=1S/C12H14N2O3/c1-3-12(8-4-6-9(15)7-5-8)10(16)14(2)11(17)13-12/h4-7,15H,3H2,1-2H3,(H,13,17)/i2D3
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| Chemical Name |
5-ethyl-5-(4-hydroxyphenyl)-3-(trideuteriomethyl)imidazolidine-2,4-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: 100 mg/mL (421.46 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 | 4.2146 mL | 21.0730 mL | 42.1461 mL | |
| 5 mM | 0.8429 mL | 4.2146 mL | 8.4292 mL | |
| 10 mM | 0.4215 mL | 2.1073 mL | 4.2146 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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