| Size | Price | Stock | Qty |
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| 100μg |
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| 1mg | |||
| Other Sizes |
| Targets |
Propofol-d17 beta-D-glucuronide is a stable isotope-labeled internal standard. Its unlabeled parent, Propofol beta-D-glucuronide, is a phase II metabolite, not a pharmacologically active drug. Propofol itself is a rapidly acting intravenous anesthetic agent that targets the GABA_A receptor (gamma-aminobutyric acid type A receptor). Propofol binds to the beta-subunit of the GABA_A receptor, allosterically potentiating the chloride channel-opening effect of GABA, leading to hyperpolarization of neurons and central nervous system depression. The glucuronide conjugate is formed in the liver (primarily by UGT1A9) and serves as a detoxification product, increasing the water solubility of propofol for efficient renal excretion. Propofol-d17 beta-D-glucuronide does not interact with the GABA_A receptor; it is a research tool used to study the metabolic clearance of propofol. The presence of seventeen deuterium atoms provides a distinct mass shift, enabling accurate quantification of the metabolite in biological samples without interference from the parent drug or other compounds.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
The in vitro biological activity of Propofol-d17 beta-D-glucuronide is not independently characterized; it is used as an internal standard. Its unlabeled parent, Propofol glucuronide, is a metabolite with no known direct pharmacological activity. In contrast, the parent drug Propofol has well-characterized in vitro activity. In HEK293 cells heterologously expressing human GABA_A receptors, Propofol (1-100 uM) potentiates GABA-induced currents (EC₅0 for potentiation: ~10 uM) and at high concentrations can directly activate the receptor. Propofol also inhibits the NMDA receptor (IC₅0 ~ 50-100 uM) and activates the GABAA-ρ (GABAC) receptor. The glucuronide metabolite does not exhibit these effects. The labeled Propofol-d17 beta-D-glucuronide is used as an internal standard in LC-MS to accurately quantify the glucuronide metabolite in in vitro systems such as human liver microsomes (HLMs) and primary hepatocyte incubations, enabling precise determination of the rate of propofol metabolism to its glucuronide. This is essential for studies of UGT1A9 activity and drug-drug interactions affecting propofol clearance. |
| ln Vivo |
The in vivo activity of Propofol-d17 beta-D-glucuronide is not evaluated; it is used as an analytical tracer. Its unlabeled parent, propofol glucuronide, is the major urinary metabolite of propofol in humans. In patients undergoing propofol anesthesia, approximately 50-70% of the administered propofol dose is recovered in urine as propofol glucuronide. The glucuronide is inactive and is cleared renally. In rats and other animal models, Propofol is rapidly metabolized to propofol glucuronide by UGT1A9 in the liver, with a plasma half-life of the glucuronide of approximately 30-60 minutes. The labeled Propofol-d17 beta-D-glucuronide is used as an internal standard in LC-MS to quantify the glucuronide metabolite in plasma and urine samples in preclinical and clinical pharmacokinetic studies. By measuring the rate of appearance and disappearance of the glucuronide, researchers can determine the metabolic clearance (CLmet) and the role of glucuronidation in propofol's overall elimination, as well as investigate the impact of co-administered drugs on UGT1A9 activity (drug-drug interactions).
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| Enzyme Assay |
A generic non-cell-based assay for Propofol-d17 beta-D-glucuronide involves its use as an internal standard in an LC-MS/MS method for quantifying propofol glucuronide in human plasma. Prepare a standard stock solution of unlabeled propofol beta-D-glucuronide in methanol (1 mg/mL). Prepare a separate stock solution of Propofol-d17 beta-D-glucuronide at the same concentration. Prepare calibration standards by spiking the unlabeled analyte into a blank matrix (e.g., charcoal-stripped human plasma) to achieve concentrations ranging from 10 to 5,000 ng/mL. Add a fixed concentration of the internal standard (e.g., 500 ng/mL) to each calibration standard. For sample preparation, perform protein precipitation by adding 200 uL of acetonitrile to 50 uL of plasma. Vortex and centrifuge at 12,000g for 10 minutes. Transfer the supernatant to an autosampler vial. For optimal recovery of the highly polar glucuronide, a solid-phase extraction (SPE) on a mixed-mode reversed-phase/anion exchange cartridge (e.g., Oasis MAX) may be used. Analyze by LC-MS/MS in negative ion mode (propofol glucuronide ionizes well in ESI-). Monitor the mass transitions: m/z 353.1 → 177.1 (for the glucuronide conjugate of propofol, loss of the glucuronic acid moiety) for the unlabeled analyte, and m/z 370.2 → 193.2 for Propofol-d17 beta-D-glucuronide. Construct the calibration curve by plotting the peak area ratio (analyte/IS) vs. the nominal concentration.
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| Cell Assay |
A standard in vitro cell-based protocol for Propofol-d17 beta-D-glucuronide is not relevant, as it is used as an analytical standard. However, a metabolism study using primary human hepatocytes can be performed to assess propofol glucuronidation. Isolate primary human hepatocytes from donor liver tissue. Culture the hepatocytes in Williams‘ Medium E supplemented with Matrigel in 6-well plates at 5×10⁵ cells/well. Treat the cells with 10-100 uM unlabeled Propofol (dissolved in DMSO, final concentration <0.1%) for 0, 1, 2, 4, 6, 8, 12, and 24 hours. At each time point, collect the culture medium and lyse the cells in 0.5% Triton X-100. For analysis, add a fixed amount of Propofol-d17 beta-D-glucuronide as internal standard to both the medium and cell lysate samples. Precipitate proteins with acetonitrile, centrifuge, and analyze the supernatant by LC-MS/MS. Quantify the concentration of propofol glucuronide produced at each time point. Calculate the intrinsic clearance (CL_int) for propofol glucuronidation (pmol/min/million cells) and the half-life of propofol in the hepatocytes. This protocol is used to study inter-individual variability in propofol metabolism and the potential for drug interactions.
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| Animal Protocol |
A typical in vivo animal protocol for Propofol-d17 beta-D-glucuronide involves a pharmacokinetic (PK) study in rats. Use male Sprague-Dawley rats (250-300 g, n = 4-5 per group). Administer a single intravenous bolus dose of unlabeled Propofol (10 mg/kg) via the tail vein, formulated as Diprivan® (1% propofol in 10% soybean oil, 2.25% glycerol, and 1.2% egg lecithin). Collect blood samples via tail vein or jugular vein catheter at various time points (0, 1, 2, 5, 10, 15, 30, 60, 90, 120, 180, 240 min) into tubes containing sodium fluoride (a pseudocholinesterase inhibitor to prevent in vitro hydrolysis) and placed on ice. Immediately centrifuge at 4degC to obtain plasma. Also collect 24-hour urine and feces samples using metabolic cages. For bioanalysis, spike plasma samples (50 uL) with a fixed amount of Propofol-d17 beta-D-glucuronide internal standard. Extract the glucuronide by protein precipitation with acetonitrile or by SPE on a C18 cartridge. Analyze by LC-MS/MS. Quantify both parent propofol and its glucuronide metabolite. Calculate PK parameters for propofol glucuronide: Cmax, Tmax, AUC, t½, CL, and the metabolic ratio (MR = AUC_glucuronide / AUC_parent). The goal of this study is to characterize the extent and rate of propofol glucuronidation as the primary pathway for its elimination.
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| ADME/Pharmacokinetics |
Propofol-d17 beta-D-glucuronide is an analytical internal standard. Its unlabeled parent, propofol glucuronide, is the major phase II metabolite of Propofol. Propofol itself has a very short plasma half-life (2-4 minutes in humans) and is eliminated primarily by the liver, with the glucuronide conjugate being its main metabolite. In humans, following a single intravenous bolus of propofol (2 mg/kg), plasma concentrations of propofol decline rapidly, while the glucuronide appears quickly (within 5 minutes) and persists longer (half-life approximately 60-90 minutes). The volume of distribution of propofol is large (3-4 L/kg) due to its high lipophilicity. The clearance of propofol (2-3 L/min) is mainly by hepatic metabolism, with >98% of the dose recovered in urine (70% as propofol glucuronide) and feces (30%) within 24 hours. The glucuronide has a relatively small volume of distribution (~0.2 L/kg) and is eliminated by the kidneys (CLrenal ~ 200 mL/min). The labeled Propofol-d17 beta-D-glucuronide allows for the precise quantification of this metabolite in PK studies, enabling researchers to assess the contribution of glucuronidation to propofol's overall elimination.
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| Toxicity/Toxicokinetics |
Propofol-d17 beta-D-glucuronide is a research-grade stable isotope-labeled compound, not a pharmaceutical drug. Its unlabeled parent, propofol glucuronide, is a metabolite with no known toxicity. Propofol itself is a widely used intravenous anesthetic with an excellent safety profile. Common adverse effects of propofol include pain at the injection site, hypotension (due to vasodilation), transient respiratory depression, and apnea. Rare but serious adverse effects include “propofol infusion syndrome” (PRIS), characterized by metabolic acidosis, rhabdomyolysis, and cardiovascular collapse, which is associated with high doses and prolonged infusion (>48 hours). The oral LD₅0 of propofol is >2,000 mg/kg in rodents. Propofol glucuronide does not contribute to these toxicities. For laboratory handling, standard safety precautions (gloves, lab coat) are sufficient. Propofol-d17 beta-D-glucuronide should be stored as a powder at -20degC in a tightly sealed container, protected from light and moisture. Solutions in DMSO can be stored at -80degC for up to 6 months. For research use only, not for human consumption.
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| References | |
| Additional Infomation |
Propofol-d17 beta-D-glucuronide is the stable isotope-labeled (fully deuterated) version of propofol beta-D-glucuronide, the major phase II (glucuronidation) metabolite of the widely used intravenous anesthetic agent Propofol (2,6-diisopropylphenol, Diprivan®). Propofol is one of the most commonly used drugs for the induction and maintenance of general anesthesia, as well as for sedation in intensive care units. It is also known for its antiemetic, antioxidant, and anticonvulsant properties. Propofol is primarily metabolized in the liver by UDP-glucuronosyltransferase (UGT) enzymes, mainly UGT1A9, to form an inactive glucuronide conjugate. This metabolite is then eliminated via the kidneys. Propofol-d17 beta-D-glucuronide is intended for research use as an internal standard for the accurate quantification of the glucuronide metabolite and its parent drug in biological samples by LC-MS/MS. This labeled compound is a critical tool for propofol pharmacokinetic studies, drug metabolism research, and forensic toxicology. For research use only, not for diagnostic or therapeutic applications.
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| Molecular Formula |
C18H26O7
|
|---|---|
| Molecular Weight |
354.394846439362
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| Exact Mass |
371.274
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| CAS # |
1683581-05-6
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| PubChem CID |
71751824
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| Appearance |
White to off-white solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
25
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| Complexity |
437
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| Defined Atom Stereocenter Count |
5
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| SMILES |
O([C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](C(=O)O)O1)O)C1C(=C([H])C([H])=C([H])C=1C([H])(C([H])([H])[H])C([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])[H]
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| InChi Key |
JZSJIASBMOIIKI-UEDRXGGNSA-N
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| InChi Code |
InChI=1S/C18H26O7/c1-8(2)10-6-5-7-11(9(3)4)15(10)24-18-14(21)12(19)13(20)16(25-18)17(22)23/h5-9,12-14,16,18-21H,1-4H3,(H,22,23)/t12-,13-,14+,16-,18+/m0/s1/i1D3,2D3,3D3,4D3,5D,6D,7D,8D,9D
|
| Chemical Name |
(2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[3,4,5-trideuterio-2,6-bis(1,1,1,2,3,3,3-heptadeuteriopropan-2-yl)phenoxy]oxane-2-carboxylic 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) |
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 | 2.8218 mL | 14.1088 mL | 28.2175 mL | |
| 5 mM | 0.5644 mL | 2.8218 mL | 5.6435 mL | |
| 10 mM | 0.2822 mL | 1.4109 mL | 2.8218 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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