| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Midazolam metabolite, phase 2 metabolic product
|
|---|---|
| ln Vitro |
For the quantification of the sedative and anesthetic drug midazolam and its main (active) metabolites 1-hydroxymidazolam, 4-hydroxymidazolam and 1-hydroxymidazolam glucuronide in human serum, human EDTA plasma, human heparin plasma and human urine a single accurate method by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) has been developed. Protein precipitation as sample preparation, without the need of a time-consuming deglucuronidation step for the quantification of 1-hydroxymidazolam glucuronide, resulted in a simple and rapid assay suitable for clinical practice with a total runtime of only 1.1 min. The four components and the isotope-labeled internal standards were separated on a C18 column and detection was performed with a triple-stage quadrupole mass spectrometer operating in positive ionization mode. The method was validated based on the "Guidance for Industry Bioanalytical Method Validation" (Food and Drug Administration, FDA) and the "Guideline on bioanalytical method validation" of the European Medicines Agency (EMA). Linearity was proven over the ranges of 5-1500 μg/L for midazolam, 1-hydroxymidazolam and 4-hydroxymidazolam and 25-5000 μg/L for 1-hydroxymidazolam glucuronide, using a sample volume of 100 μL. Matrix comparison indicated that the assay is also applicable to other human matrices like EDTA and heparin plasma and urine. Stability experiments showed good results for the stability of midazolam, 1-hydroxymidazolam and 1-hydroxymidazolam glucuronide in serum, EDTA and heparin plasma and urine stored for 7 days under different conditions. At room temperature, 4-hydroxymidazo-lam is stable for 7 days in EDTA plasma, but stable for only 3 days in serum and heparin plasma and less than 24 h in urine. All four compounds were found to be stable in serum, EDTA plasma, heparin plasma and urine for 7 days after sample preparation and for 3 freeze-thaw cycles. The assay has been applied in therapeutic drug monitoring of midazolam for (pediatric) intensive care patients.[1]
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| References | |
| Additional Infomation |
1-hydroxymidazolam beta-D-glucuronide is a beta-D-glucosiduronic acid that is beta-D-glucuronic acid in which the anomeric hydroxyl hydrogen has been replaced by a 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepin-4-yl group. It is the glucuronidated conjugate of the midazolam metabolite, 1-hydroxymidazolam. It has a role as a drug metabolite, a human urinary metabolite and a human blood serum metabolite. It is a beta-D-glucosiduronic acid, a monosaccharide derivative, an imidazobenzodiazepine, a member of monofluorobenzenes and an organochlorine compound. It is functionally related to a 1-hydroxymidazolam.
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| Molecular Formula |
C24H21CLFN3O7
|
|---|---|
| Molecular Weight |
517.89
|
| Exact Mass |
517.105
|
| CAS # |
81256-81-7
|
| PubChem CID |
133640
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.683g/cm3
|
| Boiling Point |
788.0±70.0 °C at 760 mmHg
|
| Flash Point |
430.3±35.7 °C
|
| Vapour Pressure |
0.0±2.9 mmHg at 25°C
|
| Index of Refraction |
1.724
|
| LogP |
1.12
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
36
|
| Complexity |
840
|
| Defined Atom Stereocenter Count |
5
|
| SMILES |
C1=CC=C(C(=C1)C2=NCC3=CN=C(COC4C(C(C(C(C(=O)O)O4)O)O)O)N3C5=C2C=C(C=C5)Cl)F
|
| InChi Key |
ICIUMXQTLQXWGL-QMDPOKHVSA-N
|
| InChi Code |
InChI=1S/C24H21ClFN3O7/c25-11-5-6-16-14(7-11)18(13-3-1-2-4-15(13)26)28-9-12-8-27-17(29(12)16)10-35-24-21(32)19(30)20(31)22(36-24)23(33)34/h1-8,19-22,24,30-32H,9-10H2,(H,33,34)/t19-,20-,21+,22-,24+/m0/s1
|
| Chemical Name |
(2S,3S,4S,5R,6R)-6-[[8-chloro-6-(2-fluorophenyl)-4H-imidazo[1,5-a][1,4]benzodiazepin-1-yl]methoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid
|
| Synonyms |
Mdz-glucuronide; 81256-81-7; 1-Hydroxymethylmidazolam glucuronide; 1'-Hydroxy Midazolam-beta-D-glucuronide; (2S,3S,4S,5R,6R)-6-[[8-chloro-6-(2-fluorophenyl)-4H-imidazo[1,5-a][1,4]benzodiazepin-1-yl]methoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid; 1'-Hydroxy Midazolam-b-D-glucuronide; 1'-Hydroxy Midazolam-b-D-glucuronide (1.0mg/ml in Methanol); 1'-OH MDZ glucuronide;
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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 | 1.9309 mL | 9.6546 mL | 19.3091 mL | |
| 5 mM | 0.3862 mL | 1.9309 mL | 3.8618 mL | |
| 10 mM | 0.1931 mL | 0.9655 mL | 1.9309 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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