| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
(S)-(+)-O-Desmethyl Venlafaxine-d6 has no independent pharmacological target as a stable isotope internal standard. The unlabeled (S)-(+)-O-Desmethyl Venlafaxine is an active metabolite of venlafaxine and targets the serotonin transporter (SERT) and norepinephrine transporter (NET), inhibiting the reuptake of these neurotransmitters. This results in increased synaptic levels of serotonin and norepinephrine, contributing to its antidepressant effects.
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| ln Vitro |
As a stable isotope-labeled internal standard, (S)-(+)-O-Desmethyl Venlafaxine-d6 is not tested for standalone in vitro pharmacological activity. The unlabeled (S)-O-desmethylvenlafaxine has a Ki of 52 nM for SERT and 558 nM for NET, making it a relatively balanced SNRI. In cell-based assays, the metabolite inhibits serotonin and norepinephrine uptake with IC50 values in the submicromolar range, contributing to the overall antidepressant effect of venlafaxine.
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| ln Vivo |
(S)-(+)-O-Desmethyl Venlafaxine-d6 has no independent in vivo pharmacological activity as a therapeutic agent. The unlabeled metabolite is the major active metabolite of venlafaxine, reaching steady-state plasma concentrations approximately 2-3 times higher than the parent drug. It contributes significantly to the antidepressant efficacy in patients with major depressive disorder, generalized anxiety disorder, and social anxiety disorder.
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| Enzyme Assay |
For in vitro LC-MS/MS quantification, (S)-(+)-O-Desmethyl Venlafaxine-d6 is dissolved in an appropriate solvent (methanol, water, or 0.1% formic acid) to prepare a stock solution (e.g., 1 mg/mL). The internal standard is added to biological samples (plasma, serum, urine, cell lysates) at a fixed concentration (e.g., 10-500 ng/mL). Protein precipitation is performed by adding 3-5 volumes of methanol or acetonitrile containing the internal standard. After centrifugation (10,000-15,000 rpm, 10 minutes), the supernatant is analyzed by LC-MS/MS. The analyte-to-internal standard peak area ratio is used for quantification.
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| Cell Assay |
(S)-(+)-O-Desmethyl Venlafaxine-d6 is not used as a treatment in cell-based studies but as an analytical standard. Cells (e.g., HEK293 cells expressing SERT or NET, or SH-SY5Y neuronal cells) are treated with venlafaxine or other test compounds. After the treatment period, cell lysates or culture supernatants are collected. The internal standard is added at a fixed concentration to each sample. Following protein precipitation and centrifugation, samples are analyzed by LC-MS/MS to quantify O-desmethylvenlafaxine levels and assess cellular metabolism of venlafaxine.
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| Animal Protocol |
For in vivo pharmacokinetic studies, (S)-(+)-O-Desmethyl Venlafaxine-d6 is not administered to animals independently. It is used as an internal standard for quantifying O-desmethylvenlafaxine in biological samples obtained from animals treated with venlafaxine. After collection of plasma, urine, or tissue homogenates, the internal standard is added at a fixed concentration. Samples are processed by protein precipitation or solid-phase extraction and analyzed by LC-MS/MS to determine absolute O-desmethylvenlafaxine concentrations for ADME and PK studies.
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| ADME/Pharmacokinetics |
As an internal standard, (S)-(+)-O-Desmethyl Venlafaxine-d6 has no independent pharmacokinetic parameters. The unlabeled O-desmethylvenlafaxine has a plasma half-life of approximately 10-12 hours in humans, longer than venlafaxine (∼5 hours). It is primarily eliminated renally (∼40-50% unchanged). Steady-state concentrations are achieved within 3 days of dosing. The metabolite crosses the blood-brain barrier and reaches therapeutic concentrations in the CNS. Venlafaxine is ∼27% protein bound; O-desmethylvenlafaxine is ∼30% bound.
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| Toxicity/Toxicokinetics |
(S)-(+)-O-Desmethyl Venlafaxine-d6 is a stable isotope-labeled internal standard with low toxicity as it is used at trace concentrations (ug-mg quantities). Venlafaxine and its metabolite O-desmethylvenlafaxine are generally well-tolerated at therapeutic doses. Common side effects include nausea, headache, dry mouth, dizziness, and somnolence. The deuterated version is chemically identical and poses no additional toxicity risk. Standard laboratory safety precautions apply. Not for human consumption.
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| References |
[1]. Yijin Liu, et al. Development of an enantioselective assay for simultaneous separation of venlafaxine and O-desmethylvenlafaxine by micellar electrokinetic chromatography-tandem mass spectrometry: Application to the analysis of drug-drug interaction. J Chromatogr A. 2015 Nov 13;1420:119-28.
[2]. F P Bymaste, et al. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001 Dec;25(6):871-80. |
| Additional Infomation |
(S)-(+)-O-Desmethyl Venlafaxine-d6 is not a drug but a deuterium-labeled stable isotope internal standard. It has no approved therapeutic status and is not intended for human consumption. It is used for analytical method development, method validation (AMV), Quality Controlled (QC) application for Abbreviated New Drug Application (ANDA), or during commercial production of venlafaxine. It is also used for therapeutic drug monitoring (TDM) of venlafaxine and its metabolite in clinical settings and for forensic toxicology analysis.
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| Molecular Formula |
C16H19D6NO2
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|---|---|
| Molecular Weight |
269.41
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| Exact Mass |
269.226
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| CAS # |
1062609-99-7
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| Related CAS # |
Desvenlafaxine;93413-62-8;(R)-(-)-O-Desmethyl Venlafaxine-d6;1062609-96-4
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| PubChem CID |
59807274
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
403.8±25.0 °C at 760 mmHg
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| Flash Point |
193.2±21.8 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.573
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| LogP |
2.26
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
19
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| Complexity |
266
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| Defined Atom Stereocenter Count |
1
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| SMILES |
[C@@H](C1C=CC(O)=CC=1)(C1(CCCCC1)O)CN(C([2H])([2H])[2H])C([2H])([2H])[2H]
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| InChi Key |
KYYIDSXMWOZKMP-MSPWYDFVSA-N
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| InChi Code |
InChI=1S/C16H25NO2/c1-17(2)12-15(13-6-8-14(18)9-7-13)16(19)10-4-3-5-11-16/h6-9,15,18-19H,3-5,10-12H2,1-2H3/t15-/m1/s1/i1D3,2D3
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| Chemical Name |
4-[(1S)-2-[bis(trideuteriomethyl)amino]-1-(1-hydroxycyclohexyl)ethyl]phenol
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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 | 3.7118 mL | 18.5591 mL | 37.1181 mL | |
| 5 mM | 0.7424 mL | 3.7118 mL | 7.4236 mL | |
| 10 mM | 0.3712 mL | 1.8559 mL | 3.7118 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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