Regadenoson is a selective adenosine A2A receptor agonist and coronary vasodilator used as a pharmacologic cardiac stress agent during myocardial perfusion imaging (MPI). It produces a rapid, short-duration increase in coronary blood flow, allowing differences in myocardial perfusion between normal and stenotic coronary arteries to be detected during diagnostic imaging.
Regadenoson is chemically described as adenosine, 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]-, and the marketed pharmaceutical product is formulated as regadenoson monohydrate. The anhydrous active moiety has the molecular formula C15H18N8O5 and molecular weight 390.35 g/mol, while regadenoson monohydrate has molecular weight 408.37 g/mol.
| Parameter | Details |
|---|---|
| Product Name | Regadenoson |
| CAS Number | 313348-27-5 |
| Molecular Formula – Anhydrous | C15H18N8O5 |
| Molecular Weight – Anhydrous | 390.35 g/mol |
| Molecular Formula – Monohydrate | C15H18N8O5 • H2O |
| Molecular Weight – Monohydrate | 408.37 g/mol |
| PubChem CID | 219024 |
| FDA UNII – Active Moiety | 2XLN4Y044H |
| Pharmacological Class | Adenosine receptor agonist |
| Therapeutic/Diagnostic Class | Pharmacologic cardiac stress test agent |
| Primary Target | Adenosine A2A receptor |
| Route | Intravenous |
PubChem identifies CAS 313348-27-5 for regadenoson and reports the anhydrous molecular weight as 390.35 g/mol. FDA labeling identifies the pharmaceutical drug substance as regadenoson monohydrate with molecular weight 408.37 g/mol.
Regadenoson is a purine nucleoside analogue containing an adenosine-like purine structure connected to a pyrazole carboxamide group. The active molecule contains four stereogenic centers associated with its ribose configuration.
Key chemical information:
The distinction between anhydrous regadenoson and regadenoson monohydrate is important when preparing API specifications and calculating assay on the appropriate basis.
Regadenoson is primarily used as a pharmacologic stress agent for myocardial perfusion imaging in patients who require pharmacological rather than exercise-induced coronary vasodilation.
It is particularly useful during radionuclide MPI because regadenoson increases coronary blood flow rapidly and for a relatively short duration. Areas supplied by stenotic coronary arteries receive comparatively less increase in blood flow, allowing perfusion abnormalities to be visualized.
Regadenoson is a low-affinity agonist of the A2A adenosine receptor. FDA documentation reports a Ki of approximately 1.3 µM for the A2A receptor and at least 10-fold lower affinity for the A1 receptor, with weak or negligible affinity for A2B and A3 receptors.
Activation of A2A receptors causes coronary vasodilation and increases coronary blood flow. FDA clinical pharmacology data show that average peak coronary blood-flow velocity increases to more than twice baseline approximately 30 seconds after administration and subsequently declines.
Quality control for Regadenoson API should include validated pharmaceutical analytical methods covering:
Where the API is manufactured as the monohydrate, water determination and hydrate-state control should be incorporated into the specification because the monohydrate has a molecular weight of 408.37 g/mol compared with 390.35 g/mol for the anhydrous active moiety.
Regadenoson is a synthetic small-molecule pharmaceutical API. Manufacturing involves controlled chemical synthesis followed by purification, isolation and drying/crystallization as appropriate to the specified solid form.
A pharmaceutical-grade manufacturing process should control:
For regulated API manufacture, validated analytical methods and appropriate GMP quality systems should be applied.
The molecular descriptors are based on the PubChem record for the anhydrous active moiety.
The marketed regadenoson formulation is a sterile, nonpyrogenic intravenous solution. FDA labeling describes the solution as clear and colorless. Each 1 mL contains 0.084 mg regadenoson monohydrate, equivalent to 0.08 mg regadenoson on an anhydrous basis. The labeled formulation has a pH range of 6.3–7.7.
For bulk API, packaging and storage should follow the validated manufacturer specification and stability data for the particular solid form. The storage condition of the finished injectable formulation should not automatically be presented as the storage specification for bulk API.
Typical pharmaceutical documentation may include:
A qualified Regadenoson API manufacturing program should emphasize chemical purity, control of process-related impurities and consistent control of the API's specified solid form.
Key manufacturing and quality considerations include:
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Individual Impurity | NMT 0.10% |
| Total Impurities | NMT 0.50% |
| Water Content | NMT 0.5% |