4 oh midazolam

Manufactured by Merck Group

Sourced in United States

4-OH-midazolam is a chemical compound used as a laboratory standard in pharmaceutical research and development. It is the major metabolite of the drug midazolam, which is a benzodiazepine medication. 4-OH-midazolam is commonly used as a reference standard for analytical methods and pharmacokinetic studies related to midazolam.

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Midazolam (72 citations)

4 protocols using 4 oh midazolam

Comprehensive Compound Library Analysis

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Albendazole, 1-OH-albendazole, benzydamine, phenacetin, acetaminophen, bufuralol, flutamide, diclofenac, and paclitaxel were obtained from the AstraZeneca compound library. 2-OH-bupropion, 1-OH-bufuralol, 1-OH-midazolam, 4-OH-midazolam, 4-OH-mephenytoin, 4-OH-diclofenac, 2-OH-flutamide, benzydamine N-oxide, 4-nitrocatechol, β-Nicotinamide adenine dinucleotide hydrate (NADPH) and DMSO were obtained from Sigma (St. Louis, MO, USA). Bupropion was obtained from Kemprotec Limited (Smailthorn, Carnforth, United Kingdom), midazolam from Lipomed (Cambridge, MA, USA), 6α-OH-paclitaxel from EMD Chemicals (San Diego, CA, USA), and S-mephenytoin from Toronto Research Chemicals (Toronto, ON, Canada). P-nitrophenol and potassium dihydrogen phosphate were obtained from Thermo Fisher Scientific (Gothenburg, Sweden) and dipotassium hydrogen phosphate and magnesium chloride were obtained from Merck (Kenilworth, NJ, USA). Formic acid (98–100%, analytical grade) was obtained from Merck (Darmstadt, Germany), acetonitrile from Rathburn (Walkerburn, UK), and ethanol from CCS Healthcare AB, Borlänge, Sweden. Deionized water was produced in an ELGA purification system (High Wycombe, UK).

Rubin K., Ewing P., Bäckström E., Abrahamsson A., Bonn B., Kamata S, & Grime K. (2020). Pulmonary Metabolism of Substrates for Key Drug-Metabolizing Enzymes by Human Alveolar Type II Cells, Human and Rat Lung Microsomes, and the Isolated Perfused Rat Lung Model. Pharmaceutics, 12(2), 117.

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Quantification of Midazolam Metabolites

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Midazolam (MDZ), 1’-OH-midazolam, 4’-OH-midazolam, and lorazepam (LZP) reference standards and ammonium acetate were purchased from Sigma-Aldrich (St. Louis, MO). Methanol, sodium hydroxide, and methyl-t-butyl-ether (MTBE) was purchased from Fisher Scientific (Pittsburgh, PA). Drug-free Balb-C mouse plasma was provided by Innovative Research (Novi, MI). All water used was ultrafiltered (Millipore).

Nicoli E.R., Al Eisa N., Cluzeau C.V., Wassif C.A., Gray J., Burkert K.R., Smith D.A., Morris L., Cologna S.M., Peer C.J., Sissung T.M., Uscatu C.D., Figg W.D., Pavan W.J., Vite C.H., Porter F.D, & Platt F.M. (2016). Defective Cytochrome P450-Catalysed Drug Metabolism in Niemann-Pick Type C Disease. PLoS ONE, 11(3), e0152007.

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Midazolam Metabolism and Pharmacokinetics

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Midazolam was obtained from Fujifilm Wako Pure Chemical Co. 1′‐OH Midazolam was obtained from Funakoshi Co., Ltd. 4‐OH Midazolam was obtained from Sigma‐Aldrich. Midazolam Injection (Dormicam^® Injection 10 mg; Astellas Pharma Inc.) was used for the in vivo study. Phenacetin, disodium hydrogen phosphate 12‐water, sodium dihydrogen phosphate dihydrate, potassium hydrogen phosphate, potassium dihydrogen phosphate, sucrose, Tris, EDTA‐2K, and glycerol were obtained from Fujifilm Wako Pure Chemical Co. All chemicals used for high‐performance liquid chromatography (HPLC) were HPLC grade and obtained from Fujifilm Wako Pure Chemical Co.

Togao M., Kawakami K., Otsuka J., Wagai G., Ohta‐Takada Y, & Kado S. (2020). Effects of gut microbiota on in vivo metabolism and tissue accumulation of cytochrome P450 3A metabolized drug: Midazolam. Biopharmaceutics & Drug Disposition, 41(7), 275-282.

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Hepatocyte Isolation and CYP3A4 Assay

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All buffers, media, and supplements were purchased from Life Technologies (Carlsbad, CA, USA) except for BSA (Thermofisher, Waltham, MA, USA), ascorbic acid (Sigma, St. Louis, MO, USA), collagenase (Sigma, St. Louis, MO, USA), Percoll^™ (GE, Pittsburgh, PA, USA), FBS (Hyclone, Logan, UT, USA), Matrigel^™ (BD Corning, Tewksbury, MA, USA), BCA protein assay kit (Pierce Thermofisher, Waltham, MA, USA), midazolam (Cambridge Isotope Laboratories, Andover, MA, USA), 4OH-midazolam (Sigma, St. Louis, MO, USA), troleandomycin (Enzo Life Sciences, Farmingdale, NY, USA), dexamethasone (Cayman Chemical Company, Ann Arbor, MI, USA), and diltiazem (Sigma, St. Louis, MO, USA). Multi-well cell culture plates were purchased from BD Corning (Tewksbury, MA, USA).

Pham C., Nagar S, & Korzekwa K. (2020). Numerical analysis of time dependent inhibition kinetics: comparison between rat liver microsomes and rat hepatocyte data for mechanistic model fitting. Xenobiotica; the fate of foreign compounds in biological systems, 50(11), 1301-1310.

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