| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Not applicable for the deuterated standard. The parent compound, hydroxyzine, is a first‑generation antihistamine with potent H1 histamine receptor antagonist activity. It also has anticholinergic (muscarinic receptor antagonism), anti‑emetic (central), and anxiolytic (via H1 and possibly other mechanisms) properties. It is used in research as a reference H1 antagonist and to study histaminergic pathways.
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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].
Not applicable. Hydroxyzine-d4 dihydrochloride itself is not used for measuring pharmacological activity. Unlabeled hydroxyzine is a potent H1 antagonist with a Ki of approximately 1‑10 nM. It inhibits histamine‑induced contractions in isolated guinea pig ileum and blocks histamine‑induced flare and wheal responses in vivo. Hydroxyzine also binds to M1 and M3 muscarinic receptors (Ki approx. 50‑200 nM), contributing to its anticholinergic side effects (dry mouth, blurred vision). |
| ln Vivo |
Not applicable. Hydroxyzine-d4 dihydrochloride is an analytical standard and is not used for in vivo activity assays. The parent compound hydroxyzine is used clinically for pruritus, urticaria, anxiety, and as a premedication before anesthesia. In research, it is used to study histaminergic and cholinergic pathways. The labeled standard is used in ADME studies to quantify hydroxyzine and cetirizine levels after administration of hydroxyzine.
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| Enzyme Assay |
For analytical method development, Hydroxyzine-d4 dihydrochloride is used as an internal standard. A stock solution is prepared in methanol or acetonitrile at 1 mg/mL. Calibration standards are prepared by spiking blank biological matrix (e.g., plasma, urine) with known concentrations of unlabeled hydroxyzine dihydrochloride (0.1‑1000 ng/mL) and a fixed concentration of Hydroxyzine-d4 dihydrochloride (10‑100 ng/mL). Proteins are precipitated with 3‑5 volumes of acetonitrile containing the internal standard. After centrifugation, the supernatant is evaporated under nitrogen and reconstituted in mobile phase (0.1% formic acid in water/methanol). Analysis is performed by LC‑MS/MS in MRM mode, monitoring transitions: for hydroxyzine, m/z 375.2 → 201.1 (or 375 → 165); for hydroxyzine-d4 (2‑hydroxyethoxy-d4), m/z 379.2 → 201.1 (or 379 → 165). The peak area ratio (analyte/IS) is plotted against the nominal concentration to generate a calibration curve. The method is validated for selectivity, linearity (0.1‑1000 ng/mL), accuracy, precision, and stability.
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| Cell Assay |
Hydroxyzine-d4 dihydrochloride is not used in cellular activity assays. In research settings, the parent compound hydroxyzine can be used in cell‑based assays to study H1 receptor antagonism. For example, CHO cells stably expressing the H1 receptor are loaded with Fluo‑4 AM, pre‑incubated with hydroxyzine (0.1‑1000 nM), and then stimulated with histamine (EC80). The fluorescence (ex 485 nm, em 525 nm) is measured, and the IC50 for inhibition is calculated. However, the deuterated analog is not used in such assays.
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| Animal Protocol |
Hydroxyzine-d4 dihydrochloride is used in pharmacokinetic (PK) and bioequivalence studies of hydroxyzine in animal models and humans. Animals (e.g., male Sprague‑Dawley rats, 200‑300 g) are administered an oral or intravenous dose of hydroxyzine dihydrochloride (5‑30 mg/kg for rats, 25‑100 mg for humans). Blood samples are collected at predetermined time points (0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 h). Plasma is separated, and the concentration of hydroxyzine and its active metabolite cetirizine is measured by LC‑MS/MS using Hydroxyzine-d4 dihydrochloride as an internal standard. Pharmacokinetic parameters (Cmax, Tmax, AUC, t½, clearance, Vd, oral bioavailability) are calculated by non‑compartmental analysis. For metabolite studies, the labeled standard can be used to quantify the formation of cetirizine (the carboxylic acid metabolite). The deuterium label does not alter the metabolism or PK.
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| ADME/Pharmacokinetics |
Hydroxyzine-d4 dihydrochloride (MW 451.85, C21H25D4Cl3N2O2) is a stable isotope‑labeled compound with 99 atom% deuterium at the four hydrogens on the 2‑hydroxyethoxy group. It has the same chemical and physical properties as unlabeled hydroxyzine dihydrochloride. Hydroxyzine is well absorbed orally (bioavailability ~80%), has a plasma half‑life of 10‑20 hours, and is metabolized by CYP3A4 and CYP2D6 to cetirizine (active) and other inactive metabolites. The deuterated analog is used as an internal standard and is not administered in large quantities.
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| Toxicity/Toxicokinetics |
Hydroxyzine-d4 dihydrochloride is chemically stable and non‑toxic at the concentrations used as an internal standard (ng/mL levels). The parent compound hydroxyzine is a clinically approved drug with known safety profile: common adverse effects include drowsiness, dry mouth, blurred vision, and constipation. Overdose can cause CNS depression and anticholinergic delirium. The labeled analog is not intended for human consumption. Storage: powder at -20degC for 3 years, protected from moisture.
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| References |
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| Additional Infomation |
Hydroxyzine-d4 dihydrochloride (CAS 1219805-91-0) is a stable isotope‑labeled internal standard for LC‑MS/MS quantification of hydroxyzine and its active metabolite cetirizine. Hydroxyzine is a first‑generation antihistamine used for urticaria, pruritus, and anxiety. The labeled analog is for research and analytical use only.
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| Molecular Formula |
C21H25D4CL3N2O2
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|---|---|
| Molecular Weight |
451.85
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| Exact Mass |
450.155
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| CAS # |
1219805-91-0
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| Related CAS # |
Hydroxyzine dihydrochloride;2192-20-3;Hydroxyzine;68-88-2
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| PubChem CID |
131845829
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| Appearance |
White to off-white solid powder
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| LogP |
4.535
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
28
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| Complexity |
376
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])(C([2H])([2H])OCCN1CCN(CC1)C(C2=CC=CC=C2)C3=CC=C(C=C3)Cl)O.Cl.Cl
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| InChi Key |
ANOMHKZSQFYSBR-PCOYNHINSA-N
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| InChi Code |
InChI=1S/C21H27ClN2O2.2ClH/c22-20-8-6-19(7-9-20)21(18-4-2-1-3-5-18)24-12-10-23(11-13-24)14-16-26-17-15-25;;/h1-9,21,25H,10-17H2;2*1H/i15D2,17D2;;
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| Chemical Name |
2-[2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]-1,1,2,2-tetradeuterioethanol;dihydrochloride
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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 | 2.2131 mL | 11.0656 mL | 22.1312 mL | |
| 5 mM | 0.4426 mL | 2.2131 mL | 4.4262 mL | |
| 10 mM | 0.2213 mL | 1.1066 mL | 2.2131 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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