| Size | Price | Stock | Qty |
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| Targets |
vilazodone metabolite
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| ln Vitro |
The semi-quantitative estimation of VLZ (Vilazodone) and metabolites was carried out on the basis of percent (%) count. The relative percent abundance for Vilazodone (VLZ) and each metabolite (M1-M12) formed in urine, faeces and plasma are summarized in Fig. 2 (a-c). As the metabolism studies were conducted without any reference standards, there may be uncertainty regarding the estimation of metabolites and therefore ion counts have been utilized to carry out semiquantitative estimation of metabolites.[32, 33] Based on the present study, it was observed that VLZ was found in all in vivo samples and comparatively higher percent in faeces (13.93%). This article is protected by copyright. All rights reserved. In urine, VLZ was extensively metabolized which led to the formation of nine metabolites. Metabolites M4 (10.86%) and M11 (27.02%) were the major metabolites observed in urine whereas other metabolites were detected in minor amounts. Metabolites M6 (47.7%) and M2 (11.69%) were formed at higher levels in faeces including VLZ, while other metabolites were minor. Three metabolites were detected in plasma, among which metabolite M8 (3.54%) was the only metabolite formed in higher level and other metabolites (M4 and M11) were detected in minor amounts. Minor amount of M4 and M8 metabolites were detected in both HLM and RLM.[1]
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| ln Vivo |
Vilazodone is a selective serotonin reuptake inhibitor (SSRI) used for the treatment of major depressive disorder (MDD). An extensive literature search found few reports on the in vivo and in vitro metabolism of vilazodone. Therefore, we report a comprehensive in vivo and in vitro metabolic identification and structural characterization of vilazodone using ultrahigh-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF/MS/MS) and in silico toxicity study of the metabolites.[1]
Methods: To identify in vivo metabolites of vilazodone, blood, urine and faeces samples were collected at different time intervals starting from 0 h to 48 h after oral administration of vilazodone to Sprague-Dawley rats. The in vitro metabolism study was conducted with human liver microsomes (HLM) and rat liver microsomes (RLM). The samples were prepared using an optimized sample preparation approach involving protein precipitation followed by solid-phase extraction. The metabolites have been identified and characterized by using LC/ESI-MS/MS.[1] Results: A total of 12 metabolites (M1-M12) were identified in in vivo and in vitro matrices and characterized by LC/ESI-MS/MS. The majority of the metabolites were observed in urine, while a few metabolites were present in faeces and plasma. Two metabolites were observed in the in vitro study. A semi-quantitative study based on percentage counts shows that metabolites M11, M6 and M8 were observed in higher amounts in urine, faeces and plasma, respectively.[1] Conclusions: The structures of all the 12 metabolites were elucidated by using LC/ESI-MS/MS. The study suggests that vilazodone was metabolized via hydroxylation, dihydroxylation, glucuronidation, oxidative deamination, dealkylation, dehydrogenation and dioxidation. All the metabolites were screened for toxicity using an in silico tool.[1] |
| Enzyme Assay |
In vitro metabolite generation[1]
The in vitro metabolite generation studies were performed according to reported methodology. To conduct in vitro metabolism study, 25 µl of HLM (Human Liver Microsomes) and RLM (Rat Liver Microsomes) suspensions (20 mg ml-1 ) were added to two different eppendorf tubes containing 420 µl of 100 mM phosphate buffer (pH 7.4) respectively. Microsomes were preconditioned for 5 min at 37 °C. 5 µl of 1mM stock solution of the drug was added to each tube. The metabolic reaction was initiated by addition of 50 µl of 10 mM NADPH (cofactor). Control samples consisted of phosphate buffer instead of cofactor. Initially an aliquot of 100 µl was withdrawn as zero time point sample and was quenched instantly with equal volume of chilled ACN, succeeded by vortexing. The second aliquot (400 µl) was incubated in the incubator shaker with continuous shaking (50 rpm) at 37 °C for the duration of 2 h, and later processed in similar fashion. All the samples were centrifuged at 10000 rpm for 10 min and the supernatants were subjected to solid phase extraction (SPE) for enrichment of metabolites and removal of interference. |
| Animal Protocol |
For in vivo metabolic profiling of VLZ (Vilazodone), male Sprague–Dawley rats (200-220 gm) were used.[1]
In vivo Sample preparation Vilazodone (VLZ) was orally administered to rats in the form of 0.5% carboxymethyl-cellulose suspension at a dose of 20 mg kg-1 . Animals were given access to the food after 4 h of the drug administration. Blood samples (0.2 mL) were collected from rats (n=6) in 0.5 mL eppendorf tubes through retro-orbital route according to known pharmacokinetics. The plasma was separated from the blood samples by centrifugation at 6000 rpm for 10 min at 4 °C and stored at -80 °C until analysis. Protein precipitation was done by addition of three volumes of ACN to urine and plasma followed by vortexing for 2-3 min and centrifugation at 10000 rpm for 10 min. The supernatant was concentrated via nitrogen evaporation and the remaining aqueous portion was subjected to SPE using strata C18-E cartridges. The eluted portion was submitted for analysis. The faeces and urine This article is protected by copyright. All rights reserved. samples were collected before drug administration and at intervals of 0-8, 8-24, 24-48 h post dose from another set of animals (n= 6). Sample aliquots were pooled together and stored at - 80 °C until analysis. In case of faeces, equal volumes of water and ACN were added. The mixture was vortexed to slurry which was subjected to centrifugation at 10000 rpm for 10 min and treated in a similar way like urine and plasma samples.[1] |
| References | |
| Additional Infomation |
The present study describes identification and characterization of 12 metabolites of VLZ in biological matrix (rat urine, faeces, plasma, HLM and RLM) by LC-MS/MS technique. Sample preparation was carried out by protein precipitation followed by solid phase extraction. The systematic structural characterization of the metabolites (M1-M12) was carried out by comparison of mass spectrum of the VLZ with those of metabolites and accurate mass measurement studies. Hydroxylated and dihydroxylated metabolites were formed in in vitro studies. The in vivo biotransformation pathway of VLZ includes hydroxylation, glucuronidation, dehydrogenation, oxidative deamination etc., In silico screening of metabolites was carried out using TOPKAT software. The study provides comprehensive information on the in vivo and in vitro drug metabolism when administered in rats. Structural knowledge of metabolites can be useful in developing new molecules with improved efficacy.[1]
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| Molecular Formula |
C26H26N4O3
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|---|---|
| Molecular Weight |
442.5096
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| Exact Mass |
442.2
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| CAS # |
163521-19-5
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| Related CAS # |
Vilazodone Hydrochloride;163521-08-2;Vilazodone;163521-12-8
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| PubChem CID |
11201569
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| Appearance |
White to light yellow solid powder
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| LogP |
4.631
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
730
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
RSXUEYFLDNUILS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H26N4O3/c27-16-18-4-6-23-22(13-18)19(17-28-23)3-1-2-8-29-9-11-30(12-10-29)21-5-7-24-20(14-21)15-25(33-24)26(31)32/h4-7,13-15,17,28H,1-3,8-12H2,(H,31,32)
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| Chemical Name |
5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl]-1-benzofuran-2-carboxylic acid
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| Synonyms |
5-(4-(4-(5-Cyano-1H-indol-3-yl)butyl)piperazin-1-yl)benzofuran-2-carboxylic acid; Vilazodone Carboxylic acid; Vilazodone metabolite M10; 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl]-1-benzofuran-2-carboxylic acid; 93K783WZV4; 2-Benzofurancarboxylic acid, 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-1-piperazinyl]-; 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-1-piperazinyl]-2-Benzofurancarboxylic acid;
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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) |
DMSO : ~4 mg/mL (~9.04 mM)
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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 | 2.2598 mL | 11.2992 mL | 22.5984 mL | |
| 5 mM | 0.4520 mL | 2.2598 mL | 4.5197 mL | |
| 10 mM | 0.2260 mL | 1.1299 mL | 2.2598 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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