| Size | Price | Stock | Qty |
|---|---|---|---|
| 500mg |
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| 1g |
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| Other Sizes |
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| Targets |
Midazolam metabolite
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|---|---|
| ln Vitro |
CYP3A4 and CYP3A5 metabolize midazolam to 1'- and 4-hydroxymidazolam, while UDP-glucuronosyltransferases (UGTs) further convert it to glucuronide conjugates[1].
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| Enzyme Assay |
Midazolam undergoes oxidative hydroxylation by CYP3A to its metabolites, which are excreted mainly as glucuronidated conjugates into the urine. In this study, we examined the glucuronidation of hydroxymidazolam in human liver microsomes (HLMs) and characterized the UDP-glucuronosyltransferases (UGTs) involved in 1'- and 4-hydroxymidazolam glucuronidation. Among the 12 UGT isoforms tested, the O- and N-glucuronidation of 1'-hydroxymidazolam was mediated by UGT2B4/2B7 and 1A4, respectively. In contrast, the glucuronidation of 4-hydroxymidazolam was mediated by UGT1A4. Consistent with these observations, the UGT1A4 inhibitor hecogenin and the UGT2B7 substrate diclofenac potently inhibited the N- and O-glucuronidation of 1'-hydroxymidazolam in HLMs, respectively. A correlation analysis of UGT enzymatic activity and the formation rate of glucuronide metabolites from 1'- and 4-hydroxymidazolam in 25 HLMs showed that hydroxymidazolam glucuronidation is correlated with UGT1A4-mediated lamotrigine glucuronidation and UGT2B7-mediated diclofenac glucuronidation activity. Taken together, these findings indicate that UGT1A4, 2B4, and 2B7 are major isoforms responsible for glucuronide conjugate formation from 1'- and 4-hydroxymidazolam, which are the two major oxidative metabolites of midazolam.[1]
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| ADME/Pharmacokinetics |
Metabolism / Metabolites
4-Hydroxymidazolam is a known human metabolite of midazolam. |
| Toxicity/Toxicokinetics |
Metabolism / Metabolites:
4-Hydroxymidazolam is a known human metabolite of midazolam.
|
| References |
[1]. Seo KA, et al. Metabolism of 1'- and 4-hydroxymidazolam by glucuronide conjugation is largely mediated by UDP-glucuronosyltransferases 1A4, 2B4, and 2B7. Drug Metab Dispos. 2010 Nov;38(11):2007-13.
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| Additional Infomation |
4-hydroxymidazolam is an imidazobenzodiazepine that is midazolam which is substituted by a hydroxy group at position 4. It is the minor hydroxylated metabolite of the anesthetic, midazolam. It has a role as a drug metabolite, a human blood serum metabolite and a human urinary metabolite. It is an imidazobenzodiazepine, a member of monofluorobenzenes, an organochlorine compound and an organic hydroxy compound. It is functionally related to a midazolam.
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| Molecular Formula |
C18H13CLFN3O
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|---|---|
| Molecular Weight |
341.77
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| Exact Mass |
341.073
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| CAS # |
59468-85-8
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| Related CAS # |
1'-Hydroxymidazolam-d4;1781843-10-4;1'-Hydroxymidazolam-13C3;1189677-14-2;1'-Hydroxymidazolam-13C6;1261396-36-4
|
| PubChem CID |
124449
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.44g/cm3
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| Boiling Point |
550.6ºC at 760 mmHg
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| Melting Point |
186-187ºC
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| Flash Point |
286.8ºC
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| Index of Refraction |
1.688
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| LogP |
3.25
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
24
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| Complexity |
505
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC2N3C(C)=NC=C3C(N=C(C3=CC=CC=C3F)C=2C=1)O
|
| InChi Key |
ZYISITHKPKHPKG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H13ClFN3O/c1-10-21-9-16-18(24)22-17(12-4-2-3-5-14(12)20)13-8-11(19)6-7-15(13)23(10)16/h2-9,18,24H,1H3
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| Chemical Name |
8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepin-4-ol
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| Synonyms |
4-Hydroxymidazolam; 59468-85-8; 4-Hydroxy Midazolam; 4-OH-Mdz; 8-chloro-6-(2-fluorophenyl)-1-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-4-ol; LIW2RH792R; 4H-Imidazo(1,5-a)(1,4)benzodiazepin-4-ol, 8-chloro-6-(2-fluorophenyl)-1-methyl-; 4-Hydroxy Midazolam (1.0 mg/mL in methanol);
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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 | 2.9259 mL | 14.6297 mL | 29.2594 mL | |
| 5 mM | 0.5852 mL | 2.9259 mL | 5.8519 mL | |
| 10 mM | 0.2926 mL | 1.4630 mL | 2.9259 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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