| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Targets (as internal standard): Isotope-Labeled Compounds. The parent Metolazone inhibits the Na+/Cl- cotransporter (IC50 = 0.3 uM for rat transporter) and human carbonic anhydrase VII (Ki = 2.1 nM), CAXII (Ki = 5.4 nM), and CAXIII (Ki = 15 nM).
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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].
No direct in vitro biological activity is reported for the labeled standard. The parent compound Metolazone inhibits the Na+/Cl- cotransporter, which reduces sodium and chloride reabsorption in the distal convoluted tubule, leading to increased urine output. |
| ln Vivo |
In vivo, Metolazone (0.3 and 1 mg/kg) induces fluid loss and enhances captopril-induced decreases in blood pressure in spontaneously hypertensive rats. Formulations containing metolazone are used clinically to treat high blood pressure and edema.
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| Enzyme Assay |
For cell-free assay: plasma or urine samples containing metolazone are spiked with the internal standard Metolazone-d7. After protein precipitation with acetonitrile and centrifugation, the supernatant is analyzed by LC-MS/MS. Quantitation is achieved by comparing the analyte peak area to the internal standard peak area.
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| Cell Assay |
No cell-based assays are performed with the deuterated standard. The parent metolazone is tested in vitro for ion transport inhibition using cell lines expressing the Na+/Cl- cotransporter, typically by measuring thallium or rubidium influx.
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| Animal Protocol |
Animal studies for the deuterated standard are not applicable. In vivo PK studies of unlabeled metolazone are performed in spontaneously hypertensive rats or dogs. The animals are dosed orally or intravenously, and serial blood samples are collected, processed with the internal standard, and analyzed by LC-MS/MS.
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| ADME/Pharmacokinetics |
PK properties of metolazone: oral bioavailability is variable (approx. 40-70%), peak plasma concentrations occur 2-4 hours post-dose, plasma protein binding is high (approx. 95%), and elimination half-life ranges from 6-20 hours depending on renal function. The deuterated standard is not subjected to PK analysis.
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| Toxicity/Toxicokinetics |
No toxicity data are reported for the deuterated standard. For parent metolazone, common adverse effects include electrolyte imbalances (hypokalemia, hyponatremia), dehydration, hypotension, dizziness, and gastrointestinal disturbances. The labeled compound is for research use only.
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| References | |
| Additional Infomation |
Metolazone-d7 is a research standard and not an active drug substance. It is used as a stable isotope-labeled internal standard (SIL-IS) for quality control, analytical method development, and impurity profiling in pharmaceutical manufacturing. Metolazone is FDA-approved for hypertension and edema.
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| Molecular Formula |
C16H16CLN3O3S
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|---|---|
| Molecular Weight |
372.877673149109
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| Exact Mass |
372.104
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| CAS # |
2714484-71-4
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| Related CAS # |
Metolazone;17560-51-9
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| PubChem CID |
76974425
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| Appearance |
White to off-white solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
24
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| Complexity |
594
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C(=CC2C(N(C3C([2H])=C([2H])C([2H])=C([2H])C=3C([2H])([2H])[2H])C(C)NC=2C=1)=O)S(N)(=O)=O
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| InChi Key |
AQCHWTWZEMGIFD-HRDWIZOWSA-N
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| InChi Code |
InChI=1S/C16H16ClN3O3S/c1-9-5-3-4-6-14(9)20-10(2)19-13-8-12(17)15(24(18,22)23)7-11(13)16(20)21/h3-8,10,19H,1-2H3,(H2,18,22,23)/i1D3,3D,4D,5D,6D
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| Chemical Name |
7-chloro-2-methyl-4-oxo-3-[2,3,4,5-tetradeuterio-6-(trideuteriomethyl)phenyl]-1,2-dihydroquinazoline-6-sulfonamide
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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) |
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
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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 | 2.6818 mL | 13.4091 mL | 26.8183 mL | |
| 5 mM | 0.5364 mL | 2.6818 mL | 5.3637 mL | |
| 10 mM | 0.2682 mL | 1.3409 mL | 2.6818 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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