| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
MeIQx-d3 is a stable isotope-labeled internal standard; its unlabeled parent compound, MeIQx, is not a therapeutic drug but a genotoxic foodborne carcinogen. MeIQx exerts its biological effects through metabolic activation primarily by cytochrome P450 enzymes (CYP1A2) in the liver, which converts it to N-hydroxy-MeIQx. This activated metabolite forms covalent DNA adducts, primarily at the C-8 position of guanine residues. These adducts can lead to G→T transversions and other mutations, initiating carcinogenesis, particularly in the colon, breast, and prostate. MeIQx is classified by the IARC as Group 2B “possibly carcinogenic to humans.” MeIQx-d3 is used as an internal standard to accurately quantify this potent genotoxicant in exposure assessment studies without altering its biological detection.
|
|---|---|
| ln Vitro |
In the process of developing new drugs, stable heavy isotopes of carbon, hydrogen, and other elements have been added to pharmacological molecules, mostly as quantitative tracers. Due to its potential effects on medication pharmacokinetics and metabolic properties, deuteration is a matter for worry [1]. Mouse hemoglobin covalently binds to MeIQx (0.47 mM; 0-120 min), which mouse microsomes then activate to produce metabolites [2].
The in vitro biological activity of MeIQx-d3 is not independently characterized, but its unlabeled parent, MeIQx, shows well-documented mutagenic and genotoxic activity. In the standard Ames test using Salmonella typhimurium TA98 strain, MeIQx induces frameshift mutations with extremely high potency, demonstrating specific mutagenic activity of approximately 100,000 revertants per microgram, making it one of the most potent mutagens ever tested. In human hepatoma HepG2 cells, MeIQx (0.1-50 uM) induces DNA strand breaks as measured by the alkaline Comet assay, increases micronucleus formation, and upregulates CYP1A1 and CYP1A2 gene expression. MeIQx-d3 serves as an internal standard in LC-MS to accurately quantify MeIQx concentrations in culture media, ensuring precise exposure assessment in these in vitro genotoxicity studies. |
| ln Vivo |
In male Swiss Webster mice, MeIQx (2.0-200 mg/kg; i.p.) covalently bonds to hemoglobin in a dose-dependent manner [2].
The in vivo activity of MeIQx-d3 itself is not studied; however, its unlabeled parent exhibits potent carcinogenicity in animal models. In Fischer 344 rats, chronic dietary administration of MeIQx (0.03-0.04% in diet) for 52 weeks induces a high incidence of hepatocellular carcinomas and adenomas, as well as tumors in the colon, Zymbal gland, and clitoral gland. In male mice, oral MeIQx (300 ppm) produces liver and forestomach tumors. MeIQx forms DNA adducts in various tissues, including liver, colon, kidney, and lung, as measured by 32P-postlabeling techniques. MeIQx-d3 is used as a critical internal standard for LC-MS/MS quantification of MeIQx and its DNA adducts in animal tissues, enabling precise correlation between internal dose and tumor incidence. |
| Enzyme Assay |
A generic non-cell-based assay for MeIQx-d3 is its use as an internal standard in an LC-MS/MS method for heterocyclic amines in food. Prepare standard stock solutions of unlabeled MeIQx in methanol (1 mg/mL). Prepare separate stock of MeIQx-d3 at the same concentration. Prepare calibration standards by spiking the unlabeled analyte into a blank matrix (e.g., homogenized meat) at concentrations ranging from 0.05 to 50 ng/g. Add fixed concentration of internal standard (e.g., 5 ng/g) to each standard. For sample preparation, extract with acetonitrile/water (80:20), perform cleanup using solid-phase extraction (SPE) on a mixed-mode cation exchange (MCX) cartridge. Elute with 5% ammonium hydroxide in methanol, evaporate under nitrogen, reconstitute in mobile phase. Analyze by LC-MS/MS in positive ESI mode monitoring transitions: m/z 214 → 199 for MeIQx and m/z 217 → 202 for MeIQx-d3. Generate calibration curve by plotting peak area ratio vs. nominal concentration.
|
| Cell Assay |
A standard in vitro cell-based assay for the unlabeled MeIQx uses the HepG2 human hepatoma cell line to assess DNA damage. Culture HepG2 cells in DMEM supplemented with 10% FBS and 1% penicillin/streptomycin at 37degC in a 5% CO2 incubator. Seed cells in 12-well plates at 2×10⁵ cells/well and allow to attach for 24 hours. Treat cells with increasing concentrations of unlabeled MeIQx (0.1, 1, 5, 10, 50 uM) or vehicle control (DMSO, final concentration <0.1%) for 24 hours. After treatment, harvest cells and perform the alkaline Comet assay: embed cells in low-melting agarose on slides, lyse in high-salt buffer (2.5 M NaCl, 100 mM EDTA, 10 mM Tris, 1% Triton X-100) for 1 hour at 4degC, then electrophorese at 0.7 V/cm for 20 minutes. Stain with SYBR Gold, visualize under fluorescence microscope, and quantify percent DNA in tail using CometScore software. Use MeIQx-d3 as internal standard in LC-MS to validate exposure concentrations in the culture medium.
|
| Animal Protocol |
A typical in vivo animal protocol for MeIQx-d3 is used in a carcinogenicity or DNA adduct study in F344 rats. Use male Fischer 344 rats (8-10 weeks old, n = 6-8 per group). Administer unlabeled MeIQx by oral gavage at doses of 0, 10, 30, or 100 mg/kg body weight, suspended in 0.5% carboxymethylcellulose, 5 days per week for 4 weeks. Collect 24-hour urine samples using metabolic cages at baseline and weekly intervals. At the end of the study, euthanize rats by CO2 asphyxiation and collect blood via cardiac puncture, and harvest liver, colon, and kidney tissues. Flash-freeze tissue samples in liquid nitrogen. For DNA adduct analysis, extract DNA using phenol-chloroform method, hydrolyze DNA to nucleotides, and analyze by LC-MS/MS with MeIQx-d3 as internal standard to quantify MeIQx-DNA adducts. Also measure serum levels of MeIQx using LC-MS with MeIQx-d3 as internal standard for toxicokinetic analysis.
|
| ADME/Pharmacokinetics |
MeIQx-d3 is an analytical internal standard, so its PK is the same as its unlabeled parent. MeIQx is rapidly absorbed following oral administration, reaching peak plasma concentrations (Cmax) within 1-2 hours. It is extensively distributed, with highest concentrations in the liver, kidney, and gastrointestinal tract. MeIQx is extensively metabolized by CYP1A2-mediated N-hydroxylation, followed by O-acetylation or sulfation to form DNA-reactive intermediates. The elimination half-life of MeIQx in rats is approximately 2-4 hours. Excretion occurs primarily via urine (70-80% of dose within 48 hours), with both parent compound and conjugated metabolites present. In humans, MeIQx is detected in urine after consumption of cooked meat, with a half-life of approximately 6-12 hours. MeIQx-d3 is critical for accurate quantification of this potent carcinogen in human biomonitoring studies.
|
| Toxicity/Toxicokinetics |
MeIQx-d3 is a research-grade chemical, not a drug. Its unlabeled parent, MeIQx, is a potent genotoxic carcinogen. MeIQx is classified by IARC as Group 2B “possibly carcinogenic to humans.” In long-term rodent bioassays, dietary MeIQx (0.03% in diet) produces hepatocellular carcinomas in male mice and rats with >50% incidence, as well as tumors in the colon, Zymbal gland, and clitoral gland. MeIQx is mutagenic in the Ames test (TA98) with metabolic activation, inducing >10⁵ revertants/ug. It forms DNA adducts primarily at the C-8 position of guanine, leading to G→T transversion mutations. The No-Observed-Adverse-Effect Level (NOAEL) for MeIQx in rats is 0.3 mg/kg/day for non-neoplastic effects. For laboratory handling, strict safety precautions should be used (gloves, fume hood, proper waste disposal) to avoid exposure, as MeIQx-d3 is presumed to retain the same hazardous properties. Store at -20degC in a sealed container.
|
| References | |
| Additional Infomation |
MeIQx-d3 is the stable isotope-labeled (deuterated) version of 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), one of the most mutagenic heterocyclic amines (HCAs) formed during high-temperature cooking of meat, fish, and other protein-rich foods. HCAs are produced via the Maillard reaction from creatine, amino acids, and sugars. MeIQx is classified as a possible human carcinogen (IARC Group 2B) based on sufficient evidence of carcinogenicity in animal studies. It is used as a biomarker of dietary exposure to cooked meat carcinogens in epidemiological studies investigating colorectal, breast, and prostate cancer risk. MeIQx-d3 serves as an essential internal standard for LC-MS/MS quantification of HCAs in food, urine, and plasma. This labeled compound is for research use only and is not intended for human consumption, diagnostic, or therapeutic applications.
|
| Molecular Formula |
C11H8D3N5
|
|---|---|
| Molecular Weight |
216.26
|
| Exact Mass |
216.12
|
| CAS # |
122457-31-2
|
| Related CAS # |
MeIQx;77500-04-0
|
| PubChem CID |
6914087
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.5g/cm3
|
| Boiling Point |
458.4ºC at 760 mmHg
|
| Melting Point |
>264°C (dec.)
|
| Flash Point |
231ºC
|
| Vapour Pressure |
1.38E-08mmHg at 25°C
|
| Index of Refraction |
1.776
|
| LogP |
1.988
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
0
|
| Heavy Atom Count |
16
|
| Complexity |
271
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
[2H]C([2H])([2H])N1C2=C(C3=NC(=CN=C3C=C2)C)N=C1N
|
| InChi Key |
DVCCCQNKIYNAKB-BMSJAHLVSA-N
|
| InChi Code |
InChI=1S/C11H11N5/c1-6-5-13-7-3-4-8-10(9(7)14-6)15-11(12)16(8)2/h3-5H,1-2H3,(H2,12,15)/i2D3
|
| Chemical Name |
8-methyl-3-(trideuteriomethyl)imidazo[4,5-f]quinoxalin-2-amine
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 4.6241 mL | 23.1203 mL | 46.2406 mL | |
| 5 mM | 0.9248 mL | 4.6241 mL | 9.2481 mL | |
| 10 mM | 0.4624 mL | 2.3120 mL | 4.6241 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
