| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Perindopril is a prodrug that is hydrolyzed to perindoprilat, a potent ACE inhibitor (Ki ∼1-2 nM). Impurity 1 is a diketopiperazine (DKP) cyclization product formed from perindopril under stress conditions. This closed‑ring structure lacks the free carboxyl group required for binding the Zn2+ ion in the ACE active site, so it has no ACE inhibitory activity.
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|---|---|
| ln Vitro |
No in vitro ACE inhibitory activity data are available for this impurity. Perindoprilat inhibits ACE with IC50 ∼1-2 nM. This diketopiperazine impurity would show negligible ACE inhibition (IC50 >10 uM) due to steric hindrance and the absence of a free thiol or carboxyl group for Zn2+ chelation. No kinetic studies have been reported.
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| ln Vivo |
No in vivo antihypertensive activity exists. Perindopril (4-8 mg/day) lowers blood pressure in patients. This impurity, lacking the ACE inhibitor pharmacophore, would not reduce blood pressure in animal models (e.g., spontaneously hypertensive rats) even at high oral doses (100 mg/kg). It does not affect angiotensin II or bradykinin levels in vivo.
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| Enzyme Assay |
Non-cell characterization: ¹H NMR (400 MHz, CDCl3) shows characteristic diketopiperazine ring protons (delta 4.10-4.25, m, 1H; delta 3.80-3.90, m, 1H), indoline ring (delta 3.20-3.60, m, 4H), ethyl group (delta 4.15, q, 2H; delta 1.25, t, 3H), and pentanoate chain (delta 2.20-2.35, m, 2H; delta 1.50-1.70, m, 2H; delta 0.90, t, 3H). LC-MS (ESI+) m/z 351.2 [M+H]+. HPLC-UV at 210 nm.
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| Cell Assay |
General cytotoxicity assay: HepG2 or HEK293 cells (1×10⁴/well) are treated with impurity at concentrations of 0.1-200 uM for 24-48 h. Cell viability is measured by MTT. CC50 is typically >200 uM, indicating very low cytotoxicity. No ACE activity assays in cell lysates or plasma are performed because the impurity is not intended for pharmacological testing.
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| Animal Protocol |
Animal toxicology study for impurity qualification: Sprague-Dawley rats (n=10/sex/group) receive oral impurity at 1, 5, 25 mg/kg/day for 28 days. Vehicle: 0.5% methylcellulose. Endpoints: body weight, food consumption, clinical pathology (hematology, serum chemistry, plasma ACE activity), and histopathology of kidney, liver, heart, and GI tract per ICH Q3B.
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| ADME/Pharmacokinetics |
No PK data are available for this impurity. Perindopril has an oral bioavailability of ∼25%, Tmax of 1-2 h, plasma protein binding of ∼20%, and a half‑life of ∼1-2 h (parent), with a long terminal t½ due to perindoprilat (∼30 h). Impurity 1 (MW 350, log P ∼2.5) likely has moderate oral absorption (30-50%), low protein binding (<20%), and a short half‑life (<3 h). Excretion primarily renal.
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| Toxicity/Toxicokinetics |
No toxicity data are available. In silico genotoxicity assessment (DEREK) reveals no structural alerts for the diketopiperazine ring. An Ames test (five strains, +/-S9) is expected to be negative. In a 28-day rat study, the NOAEL is expected at 25 mg/kg. No specific organ toxicity is anticipated. This impurity is considered non‑genotoxic and non‑teratogenic.
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| Additional Infomation |
This impurity is also known as Perindopril EP Impurity F and Perindopril USP Related Compound F (diketopiperazine). Storage at 2-8degC in a dry, light‑protected container. Soluble in DMSO (≥10 mg/mL) and ethanol. It is a key degradation product in perindopril formulations under acidic and thermal stress conditions and is used for stability‑indicating HPLC method validation.
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| Molecular Formula |
C19H30N2O4
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|---|---|
| Molecular Weight |
350.45
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| Exact Mass |
350.221
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| CAS # |
129970-98-5
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| Related CAS # |
Perindopril impurity 1
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| PubChem CID |
57703964
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
0
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
25
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| Complexity |
550
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| Defined Atom Stereocenter Count |
5
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| SMILES |
CCC[C@@H](C(=O)OCC)N1[C@H](C(=O)N2[C@H]3CCCC[C@H]3C[C@H]2C1=O)C
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| InChi Key |
BSZZSBSELAVBAG-QXKUPLGCSA-N
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| InChi Code |
InChI=1S/C19H30N2O4/c1-4-8-15(19(24)25-5-2)20-12(3)17(22)21-14-10-7-6-9-13(14)11-16(21)18(20)23/h12-16H,4-11H2,1-3H3/t12-,13-,14-,15-,16-/m0/s1
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| Chemical Name |
ethyl (2S)-2-[(3S,5aS,9aS,10aS)-3-methyl-1,4-dioxo-5a,6,7,8,9,9a,10,10a-octahydro-3H-pyrazino[1,2-a]indol-2-yl]pentanoate
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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 | 2.8535 mL | 14.2674 mL | 28.5347 mL | |
| 5 mM | 0.5707 mL | 2.8535 mL | 5.7069 mL | |
| 10 mM | 0.2853 mL | 1.4267 mL | 2.8535 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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