| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Targets |
Target: Isotope-Labeled Compounds / Pharmaceutical Impurity Standard. The parent compound, Hydrochlorothiazide, is a thiazide diuretic that inhibits the Na+/Cl- cotransporter in the distal convoluted tubule of the kidney, increasing urine output and lowering blood pressure. The 4-nitroso impurity is classified as a nitrosamine, a class of compounds with potential carcinogenic risk.
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|---|---|
| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[7].
No in vitro biological activity is reported for the labeled standard, as it is intended solely for analytical quality control. The unlabeled 4-Nitroso hydrochlorothiazide is a nitrosamine impurity that is monitored and controlled in pharmaceutical drug substance and drug product to ensure patient safety, as long-term exposure to nitrosamines is associated with an increased risk of cancer in regulatory toxicology studies. |
| ln Vivo |
No in vivo studies are performed with the labeled impurity standard, as it is not intended for therapeutic administration. The parent Hydrochlorothiazide has well-documented in vivo efficacy as an antihypertensive and diuretic agent. The nitrosamine impurity is a potential genotoxic impurity and is not used for in vivo efficacy studies.
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| Enzyme Assay |
For cell-free assay (QC/analytical): the reference standard is dissolved in an appropriate diluent (e.g., methanol or acetonitrile). The solution is injected into an LC-MS/MS or HPLC-UV system equipped with a C18 column. A calibration curve is prepared using the labeled standard to quantify the level of the unlabeled nitrosamine impurity in hydrochlorothiazide drug substance or formulated product. Isotope dilution mass spectrometry is used to correct for matrix effects.
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| Cell Assay |
No cell-based assays are performed with this standard. It is exclusively a chemical reference standard used in quality control laboratories for pharmaceutical testing. The labeled compound is not intended for biological evaluation in cells or tissues.
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| Animal Protocol |
No animal studies are conducted with the labeled internal standard. The standard is used for the analysis of samples from stability studies or bioequivalence studies of Hydrochlorothiazide, but the labeled compound itself is not administered to animals. The unlabeled drug is tested in animal models of hypertension.
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| ADME/Pharmacokinetics |
PK properties are not reported for the labeled impurity standard. The parent Hydrochlorothiazide has an oral bioavailability of approximately 60-70%, a Tmax of 1-2 hours, an elimination half-life of 6-12 hours, and is excreted unchanged in the urine. The labeled standard is used to measure the concentration of the nitrosamine impurity in drug products, not to characterize its own ADME properties.
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| Toxicity/Toxicokinetics |
No toxicity data are reported for the labeled standard. The unlabeled 4-Nitroso hydrochlorothiazide is considered a potential genotoxic impurity and is controlled in pharmaceutical products to levels below the acceptable intake (AI) limit (e.g., 96 ng/day for nitrosamines per ICH M7(R1) guidelines). Chronic exposure to nitrosamines is associated with carcinogenic risk in animal models.
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| References | |
| Additional Infomation |
4-Nitroso hydrochlorothiazide-13C,15N2,d2 is a research standard and is not approved for clinical use. It is used for analytical method development, method validation (AMV), and Quality Control (QC) applications in support of Abbreviated New Drug Applications (ANDA) or during commercial production of Hydrochlorothiazide. It is required for compliance with regulatory guidelines on nitrosamine impurities (e.g., FDA, EMA). The unlabeled Hydrochlorothiazide is FDA-approved for hypertension and edema.
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| Molecular Formula |
C613CH5D2CLN215N2O5S2
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|---|---|
| Molecular Weight |
331.73
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| Appearance |
White to off-white solid powder
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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 | 3.0145 mL | 15.0725 mL | 30.1450 mL | |
| 5 mM | 0.6029 mL | 3.0145 mL | 6.0290 mL | |
| 10 mM | 0.3015 mL | 1.5072 mL | 3.0145 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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