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| Other Sizes |
| Targets |
The biological activity of the labeled compound (Z)-10-Hydroxynortriptyline-d3 itself is not assessed in standard pharmacological assays. However, the non-labeled parent (Z)-10-Hydroxynortriptyline is the active metabolite of nortriptyline. As a secondary amine TCA, its primary pharmacological target is the presynaptic norepinephrine transporter (NET). By inhibiting NET, it prevents the reuptake of norepinephrine from the synaptic cleft, thereby enhancing noradrenergic neurotransmission. It also exhibits antagonistic activity at histamine H1, muscarinic acetylcholine, and serotonin (5-HT2) receptors.
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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[1].
The non-labeled parent compound, (Z)-10-Hydroxynortriptyline, retains the active pharmacological profile of nortriptyline, contributing to its antidepressant effects through norepinephrine reuptake inhibition. As a tricyclic antidepressant (TCA), it is used to relieve the symptoms of depression. The labeled version (Z)-10-Hydroxynortriptyline-d3 has no biological activity of its own and is used solely for analytical quantification. |
| Enzyme Assay |
The compound serves as an analytical standard; thus, no classical enzyme/receptor binding assays are performed on it. The relevant assay is for the parent metabolite, (Z)-10-Hydroxynortriptyline, which involves a radioligand binding assay to determine its affinity for the norepinephrine transporter (NET). Membranes from cells expressing human NET are incubated with [3H]-nisoxetine in the presence of varying concentrations of the non-labeled analyte. After incubation and filtration to separate bound from free ligand, the Kd value is calculated.
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| Cell Assay |
For the analysis of biological samples, (Z)-10-Hydroxynortriptyline-d3 is used as an internal standard. Plasma samples (e.g., from clinical or preclinical studies) are spiked with the d3-internal standard and subjected to protein precipitation or solid-phase extraction (SPE). The supernatant is analyzed by LC-MS/MS, where the analyte and IS are detected in multiple reaction monitoring (MRM) mode (e.g., m/z 280.2 for analyte and m/z 283.2 for the d3-IS). Peak area ratios are used for precise quantification of the parent analyte.
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| Animal Protocol |
(Z)-10-Hydroxynortriptyline is a known human metabolite of nortriptyline. In preclinical pharmacokinetic studies, nortriptyline or its metabolites are typically administered to rodents (rats or mice) to assess metabolic pathways. Blood samples are collected at various time points, and (Z)-10-Hydroxynortriptyline-d3 is added to these samples as an internal standard before LC-MS/MS analysis to determine the PK profile and metabolite concentrations of the parent drug. This deuterated standard itself is not administered.
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| ADME/Pharmacokinetics |
The non-labeled parent compound (nortriptyline) is extensively metabolized in the liver, primarily via CYP2D6, to (Z)- and (E)-10-hydroxynortriptyline. It has high plasma protein binding (approx. 90-95%) and a variable half-life dependent on CYP2D6 genotype (extensive metabolizers: 15-30 hours; poor metabolizers: up to 50 hours). The (Z)-metabolite is pharmacologically active. The labeled standard has identical physical properties but is used for analytical calibration.
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| Toxicity/Toxicokinetics |
(Z)-10-Hydroxynortriptyline-d3 is for research use only (RUO) and is not for human therapeutic use. The parent drug nortriptyline has a known toxicity profile typical of TCAs, including cardiac conduction abnormalities (QT prolongation), anticholinergic effects (dry mouth, blurred vision, constipation), sedation, and risk of toxicity in overdose. The labeled standard is considered non-toxic at the trace concentrations used for analytical purposes and is not a clinical drug.
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| References |
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216.
[2]. Shimoda K, et al. The impact of CYP2C19 and CYP2D6 genotypes on metabolism of amitriptyline in Japanese psychiatric patients. J Clin Psychopharmacol. 2002 Aug;22(4):371-8. |
| Additional Infomation |
(Z)-10-Hydroxynortriptyline-d3 is a research-grade stable isotope-labeled chemical, not a clinical drug candidate. It serves as a critical analytical reference standard for mass spectrometry-based quantification in pharmacokinetic and bioequivalence studies of nortriptyline-containing formulations. Nortriptyline is a FDA-approved tricyclic antidepressant used to treat major depressive disorder, and its metabolism is a classic example of CYP2D6 pharmacogenetics. This product is for research use only (RUO).
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| Molecular Formula |
C19H18D3NO
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| Molecular Weight |
282.40
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| Related CAS # |
(Z)-10-Hydroxynortriptyline;47132-19-4
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| Appearance |
White to light yellow 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 | 3.5411 mL | 17.7054 mL | 35.4108 mL | |
| 5 mM | 0.7082 mL | 3.5411 mL | 7.0822 mL | |
| 10 mM | 0.3541 mL | 1.7705 mL | 3.5411 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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