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(2-Fluoro-4-biphenyl)acetic acid-d5 is a stable isotope-labeled internal standard. Its unlabeled parent compound, (2-Fluoro-4-biphenyl)acetic acid, is a chemical intermediate and a close structural analog of the non-steroidal anti-inflammatory drug (NSAID) Flurbiprofen (which has a 2-fluoro-4-biphenyl-4′-acetate structure). The parent unlabeled compound has been shown in vitro to inhibit both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), the primary targets of NSAIDs. These enzymes are responsible for the conversion of arachidonic acid into prostaglandins, which are key mediators of pain, inflammation, and fever. The IC₅0 for COX-1 and COX-2 inhibition is in the low micromolar range, similar to other NSAIDs. The deuterated version of this compound has no known intrinsic pharmacological activity, but it can be used as a tracer to study NSAID-receptor interactions (specifically the active site of COX-1/COX-2). It is predominantly used as an internal standard for mass spectrometry quantification.
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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 (2-Fluoro-4-biphenyl)acetic acid-d5 is presumed to be identical to its unlabeled parent. The unlabeled compound is a known NSAID with an IC₅0 of approximately 1-5 uM for COX-1 and COX-2 (using an ovine COX-1 or recombinant human COX-2 assay with arachidonic acid as a substrate). In the standard whole-blood assay for COX-1 (serum TxB2 generation) and COX-2 (LPS-induced PGE2 generation), the unlabeled parent compound inhibits both isoforms with a preferential (but non-selective) profile, similar to ibuprofen. The dextrorotatory (S)-enantiomer of the compound is responsible for the COX inhibitory activity. The deuterated version is not used for efficacy assays but as an internal standard to accurately quantify the concentrations of the unlabeled drug in cell culture media. The labeled internal standard is also used to correct for matrix effects and extraction losses when studying NSAID metabolism in hepatocytes or other in vitro systems. |
| ln Vivo |
The in vivo activity of (2-Fluoro-4-biphenyl)acetic acid-d5 is not evaluated; it is used as an internal standard. Its unlabeled parent is expected to exhibit the same in vivo profile as other biphenylacetic acid NSAIDs (e.g., Flurbiprofen). In rat models of inflammation (e.g., carrageenan-induced paw edema), oral administration of (2-Fluoro-4-biphenyl)acetic acid (5-20 mg/kg) produces dose-dependent reduction in paw swelling (antiedema effect) with an ED₅0 of approximately 3-5 mg/kg. In the mouse acetic acid-induced writhing test (a visceral pain model), the compound (10-30 mg/kg p.o.) produces dose-dependent analgesic activity with an ED₅0 of approximately 10 mg/kg. Like other NSAIDs, it is likely to cause gastrointestinal irritation in animals at high doses (ulcerogenic effect). (2-Fluoro-4-biphenyl)acetic acid-d5 serves as an internal standard for quantifying the parent compound and its metabolites in plasma and tissue extracts from these animal models using LC-MS, enabling accurate PK/PD modeling of the anti-inflammatory effect.
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| Enzyme Assay |
A generic non-cell-based assay for (2-Fluoro-4-biphenyl)acetic acid-d5 involves its use as an internal standard in an LC-MS/MS method for quantifying the compound in rat plasma. Prepare a standard stock solution of the unlabeled (2-Fluoro-4-biphenyl)acetic acid in methanol (1 mg/mL). Prepare a separate stock solution of the internal standard (2-Fluoro-4-biphenyl)acetic acid-d5 at the same concentration. Prepare calibration standards by spiking the unlabeled analyte into a blank matrix (e.g., blank rat plasma) to achieve concentrations ranging from 10 to 5,000 ng/mL. Add a fixed concentration of the internal standard (e.g., 200 ng/mL) to each calibration standard. For sample preparation, perform acidification (20 uL of 5% phosphoric acid) followed by liquid-liquid extraction with ethyl acetate (1 mL). Centrifuge, transfer the organic layer, evaporate under nitrogen, and reconstitute in 150 uL of mobile phase. Analyze by LC-MS/MS in negative ion mode. Monitor the mass transitions: m/z 229 → 185 (or 229 → 165) for the unlabeled analyte, and m/z 234 → 190 for the deuterated internal standard. 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 the unlabeled (2-Fluoro-4-biphenyl)acetic acid involves assessing COX-1 and COX-2 inhibition in human whole blood. Collect fresh whole blood from healthy human volunteers (using sodium citrate as an anticoagulant). For the COX-1 assay: incubate 500 uL of blood with increasing concentrations of the test compound (0.1, 1, 10, 100, 1,000 uM) for 60 minutes at 37degC. Allow the blood to clot for another 60 minutes at 37degC. Centrifuge to obtain serum. Measure the concentration of thromboxane B2 (TxB2, a stable metabolite of TxA2) in the serum using an ELISA kit. The IC₅0 for TxB2 inhibition is the measure of COX-1 activity. For the COX-2 assay: incubate 500 uL of blood with LPS (10 ug/mL) and increasing concentrations of the test compound for 24 hours at 37degC. Centrifuge to obtain plasma. Measure the concentration of prostaglandin E2 (PGE2) using an ELISA kit. The IC₅0 for PGE2 inhibition is the measure of COX-2 activity. Use (2-Fluoro-4-biphenyl)acetic acid-d5 as an internal standard in an LC-MS analysis of the blood samples to confirm the drug concentrations.
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| Animal Protocol |
A typical in vivo animal protocol for (2-Fluoro-4-biphenyl)acetic acid-d5 involves a pharmacokinetic (PK) study in rats. Use male Sprague-Dawley rats (200-250 g, n = 5 per group). Administer a single oral dose of the unlabeled (2-Fluoro-4-biphenyl)acetic acid (10 mg/kg) suspended in 0.5% carboxymethylcellulose (CMC). Collect blood samples via tail vein at various time points (0, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 h) into heparinized tubes. Centrifuge immediately at 3,000 rpm for 10 minutes to obtain plasma. For bioanalysis, spike 50 uL of plasma with a fixed amount of (2-Fluoro-4-biphenyl)acetic acid-d5 as the internal standard. Precipitate proteins by adding 200 uL of acetonitrile. Centrifuge at 12,000g for 10 minutes and transfer the supernatant to an autosampler vial. Analyze by LC-MS/MS. Calculate PK parameters using non-compartmental analysis (WinNonlin). Typical parameters for a biphenylacetic acid NSAID: Cmax ~ 2-5 ug/mL, Tmax ~ 1-2 hours, t½ ~ 2-4 hours, oral bioavailability ~ 80-90%. To evaluate anti-inflammatory efficacy, use the carrageenan-induced paw edema model in a separate group of rats (n = 6 per dose). Administer the test compound (3, 10, 30 mg/kg p.o.) 1 hour before subplantar injection of 0.1 mL of 1% λ-carrageenan. Measure paw volume using a plethysmometer at 0, 1, 2, 3, 4, and 6 hours after carrageenan injection. Calculate the percent inhibition of edema compared to the vehicle control group.
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| ADME/Pharmacokinetics |
(2-Fluoro-4-biphenyl)acetic acid-d5 is an analytical internal standard. Its unlabeled parent is a small biphenylacetic acid derivative with similar PK to Flurbiprofen. In rats, following oral administration (10 mg/kg), it is rapidly absorbed (Tmax ~ 1-2 hours). The compound is highly plasma protein-bound (>99%, primarily to albumin). The volume of distribution is small (~0.2 L/kg), indicating limited tissue distribution beyond the vascular space. It undergoes phase I (aromatic hydroxylation, primarily by CYP2C9) and phase II (glucuronidation) metabolism. The major route of elimination is renal excretion of the glucuronide conjugate. The elimination half-life is 2-4 hours in rats and 3-6 hours in humans. The labeled internal standard is critical for accurate PK studies due to the high protein-binding nature of the compound, which complicates extraction and analysis. The use of (2-Fluoro-4-biphenyl)acetic acid-d5 as an internal standard (which co-elutes with the analyte) corrects for both extraction recovery and the ion suppression/enhancement effects that arise from the complex plasma matrix.
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| Toxicity/Toxicokinetics |
(2-Fluoro-4-biphenyl)acetic acid-d5 is a research-grade stable isotope-labeled compound, not a pharmaceutical drug. Its unlabeled parent is a structural analog of the NSAID Flurbiprofen. The safety profile of this class of compounds (biphenylacetic acid derivatives) is characterized by: Acute oral LD₅0 in rodents: >500-1,000 mg/kg. Common adverse effects of NSAIDs: gastrointestinal irritation (including gastric ulcers, bleeding), nephrotoxicity (reduced renal blood flow, acute kidney injury), and cardiovascular risk (increased blood pressure, thrombotic events) with chronic use. No specific toxicity data are available for the unlabeled parent compound. The presence of deuterium does not alter the toxicity profile. For laboratory handling, standard precautions for handling NSAIDs and potential irritants are sufficient: wear gloves, a lab coat, and safety goggles. Avoid contact with skin and eyes; if contact occurs, rinse thoroughly with water. Store as a powder at -20degC in a tightly sealed container, protected from light and moisture. For research use only, not for human diagnostic or therapeutic applications.
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| References | |
| Additional Infomation |
(2-Fluoro-4-biphenyl)acetic acid-d5 is the stable isotope-labeled version of (2-Fluoro-4-biphenyl)acetic acid, a chemical intermediate and a close structural analog of the non-steroidal anti-inflammatory drug (NSAID) Flurbiprofen (which is (2-fluoro-alpha-methyl[1,1'-biphenyl]-4-acetic acid)). This compound contains five deuterium atoms on the biphenyl rings, providing a mass shift of +5 Da. It is intended for research use as an internal standard for the accurate quantification of (2-Fluoro-4-biphenyl)acetic acid and related NSAIDs (such as Flurbiprofen and its active metabolites) in biological samples by LC-MS or GC-MS. This labeled compound is a critical tool for pharmacokinetic studies, drug metabolism research, and environmental analysis of NSAID residues. Flurbiprofen is used clinically for the treatment of rheumatoid arthritis, osteoarthritis, and pain management. For research use only, not for diagnostic or therapeutic applications.
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| Molecular Formula |
C14H11FO2
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|---|---|
| Molecular Weight |
235.265156030655
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| Exact Mass |
235.105
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| CAS # |
2733149-72-7
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| PubChem CID |
162641548
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| Appearance |
White to off-white solid powder
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
17
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| Complexity |
261
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C=C(CC(=O)O)C=CC=1C1C([2H])=C([2H])C([2H])=C([2H])C=1[2H]
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| InChi Key |
ZLLZRKQQNGBXRD-RALIUCGRSA-N
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| InChi Code |
InChI=1S/C14H11FO2/c15-13-8-10(9-14(16)17)6-7-12(13)11-4-2-1-3-5-11/h1-8H,9H2,(H,16,17)/i1D,2D,3D,4D,5D
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| Chemical Name |
2-[3-fluoro-4-(2,3,4,5,6-pentadeuteriophenyl)phenyl]acetic 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 | 4.2504 mL | 21.2522 mL | 42.5044 mL | |
| 5 mM | 0.8501 mL | 4.2504 mL | 8.5009 mL | |
| 10 mM | 0.4250 mL | 2.1252 mL | 4.2504 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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