| Targets |
As an impurity reference, this compound does not have a defined pharmacological target. Ticagrelor, the parent drug, is a reversible, direct‑acting antagonist of the P2Y12 receptor on platelets, which is a G protein‑coupled receptor (GPCR) that plays a central role in adenosine diphosphate (ADP)‑induced platelet activation and aggregation. The cyclopropylamine core is a key structural motif in ticagrelor, and this compound may have structural similarity but is not intended to have P2Y12 antagonist activity.
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|---|---|
| ln Vitro |
No specific in vitro activity data are available for this impurity. It serves as a reference standard to ensure the purity of ticagrelor drug substance, rather than as a pharmacologically active compound. The (1R,2S) cyclopropylamine stereochemistry and the 3,4‑difluorophenyl group are important for the activity of ticagrelor and related compounds.
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| ln Vivo |
The compound is not used in vivo for therapeutic purposes. As a process‑related impurity, it may be present at trace levels in ticagrelor drug substance and product, but it is not administered as an active agent. Its role is solely in pharmaceutical quality control.
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| Enzyme Assay |
Non‑cell‑based experiments for this compound are analytical. A typical HPLC method for impurity profiling uses a C18 reverse‑phase column (4.6 × 250 mm, 5 um) with a mobile phase of acetonitrile and 0.1% phosphoric acid in water (gradient elution 30→80% acetonitrile over 20 min) at 1.0 mL/min, with UV detection at 254 nm. LC‑MS in positive ESI mode shows the cation [M]+ of the cyclopropylamine at m/z 170.1 and the anion can be detected in negative mode at m/z 151.0 (mandelate). The mandelate counterion also gives a characteristic ¹H NMR signature (methine proton at delta 4.9 ppm, s). The compound has a flash point of 218.5 degC (closed cup) and is stored at -20 degC, protected from light. Purity is typically ≥98% from commercial suppliers.
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| Cell Assay |
Cell‑based assays are not applicable for this impurity. It is a reference material and is not intended for cellular evaluation. Any cell‑based studies would be performed on the parent drug ticagrelor, not on its impurities. Ticagrelor is tested for P2Y12 antagonism using washed human platelets or CHO cells expressing the human P2Y12 receptor, measuring ADP‑induced platelet aggregation or calcium flux. This impurity is not tested.
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| Animal Protocol |
In vivo animal experiments are not conducted for this impurity. For the parent drug ticagrelor, a standard protocol in a rat model of arterial thrombosis involves oral administration of ticagrelor (10-30 mg/kg) followed by ferric chloride‑induced injury of the carotid artery, and measurement of time to occlusion. Ticagrelor significantly prolongs occlusion time. This impurity is not administered in animals.
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| ADME/Pharmacokinetics |
Pharmacokinetic data are not applicable for this impurity. If present in a formulation, it would be at trace levels only. Based on its structure (molecular weight 321.32, cation log P ~1.5-2.0), the cyclopropylamine portion is moderately lipophilic, while the mandelate anion is polar. The compound is a solid at room temperature and is stored at -20 degC, protected from light.
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| Toxicity/Toxicokinetics |
The toxicity profile of this compound has not been characterized. GHS hazard classification: H315 (Causes skin irritation), H319 (Causes serious eye irritation). Precautionary statements: P264, P280, P302+P352, P305+P351+P338, P321, P332+P317, P337+P317, P362+P364. The compound is an irritant and should be handled with care. Standard safety precautions apply: handle in a well‑ventilated area (fume hood) with appropriate PPE (lab coat, gloves, safety goggles).
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| Additional Infomation |
Additional information: The compound has an EC number of 619‑507‑9. It is also known as Ticagrelor Impurity E, (1R,2S)‑2‑(3,4‑difluorophenyl)cyclopropanamine (R)‑mandelate. The product is for research and analytical use only, not for human or veterinary use. It is used as a reference standard for pharmaceutical impurity testing of ticagrelor (Brilinta®). Synonyms include (1R,2S)‑2‑(3,4‑difluorophenyl)cyclopropanaminium (2R)‑hydroxy(phenyl)ethanoate.
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| Molecular Formula |
C17H17F2NO3
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|---|---|
| Molecular Weight |
321.32
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| Exact Mass |
321.118
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| CAS # |
376608-71-8
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| PubChem CID |
9944965
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
23
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| Complexity |
312
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C1[C@H]([C@@H]1N)C2=CC(=C(C=C2)F)F.C1=CC=C(C=C1)[C@H](C(=O)O)O
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| InChi Key |
GUESUQPLVFMJIT-KLTOLQSASA-N
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| InChi Code |
InChI=1S/C9H9F2N.C8H8O3/c10-7-2-1-5(3-8(7)11)6-4-9(6)12;9-7(8(10)11)6-4-2-1-3-5-6/h1-3,6,9H,4,12H2;1-5,7,9H,(H,10,11)/t6-,9+;7-/m01/s1
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| Chemical Name |
(2R)-2-hydroxy-2-phenylacetic acid;trans-(1R,2S)-2-(3,4-difluorophenyl)cyclopropan-1-amine
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| Synonyms |
Ticargul intermediate 7 (standard)
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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 | 3.1122 mL | 15.5608 mL | 31.1216 mL | |
| 5 mM | 0.6224 mL | 3.1122 mL | 6.2243 mL | |
| 10 mM | 0.3112 mL | 1.5561 mL | 3.1122 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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