Sacubitril Calcium, also known as Sacubitril Hemicalcium Salt, AHU-377 Calcium Salt or AHU-377 Hemicalcium Salt, is a calcium salt form of sacubitril that is used in pharmaceutical development and manufacturing, particularly as an important intermediate associated with sacubitril-based cardiovascular medicines. The compound is identified by CAS No. 1369773-39-6 and is registered in the FDA Global Substance Registration System under UNII 8F45HCQ47Q.
Sacubitril is a neprilysin inhibitor prodrug. Following administration, sacubitril is converted to its active metabolite sacubitrilat, which inhibits neprilysin and consequently affects the breakdown of natriuretic peptides and several vasoactive peptides. Sacubitril is widely recognized as an important component of sacubitril/valsartan therapy used in cardiovascular medicine.
Chemically, Sacubitril Calcium is a hemicalcium salt with a 2:1 sacubitril-to-calcium stoichiometry. FDA GSRS represents the substance as 2C24H28NO5·Ca, while PubChem gives the equivalent complete formula as C48H56CaN2O10. Its full molecular weight is approximately 861.04 g/mol. Some commercial databases express the empirical formula as C24H28NO5·0.5Ca with a formula weight of approximately 430.52 g/mol. These are two representations of the same 2:1 hemicalcium salt and should not be confused as different substances.
The calcium salt is associated with the development and manufacturing route of sacubitril-based pharmaceutical substances. Patent literature describes Sacubitril Hemicalcium Salt as a starting material for producing sacubitril and subsequently preparing other pharmaceutical salt forms and sacubitril-containing drug substances.
Sacubitril Calcium has the molecular formula C48H56CaN2O10, a molecular weight of approximately 861.04 g/mol, and four defined stereocenters in the registered molecular structure. Its systematic chemical identity describes a calcium salt containing two stereochemically defined sacubitril-derived anionic components coordinated with calcium.
Commercial reference sources describe Sacubitril Calcium as a crystalline or powder material, generally white to beige in appearance. Reported physical data include decomposition above approximately 140°C, although physical properties can vary according to solid form, hydration state and analytical conditions.
Sacubitril Calcium has particular importance in pharmaceutical intermediate manufacturing and sacubitril-related drug-substance synthesis. It is used as an intermediate or starting material in processes involving sacubitril and sacubitril/valsartan pharmaceutical substances.
Patent literature demonstrates that Sacubitril Calcium can be converted to sacubitril under controlled chemical processing conditions. Other patent processes use Sacubitril Hemicalcium Salt as a starting material for preparing amorphous sacubitril/valsartan sodium forms.
For pharmaceutical manufacturers, control of chemical purity, stereochemistry, related substances, residual solvents, moisture, calcium content and other critical quality attributes is important because structurally related impurities can arise during synthesis. An analytical patent specifically describes an HPLC method capable of separating and determining multiple known and unknown impurities in Sacubitril Calcium.
Quality control of Sacubitril Calcium may include identification by spectroscopic techniques, chromatographic assay and related-substance analysis, moisture determination, inorganic residue testing, elemental analysis and appropriate physical characterization.
A published analytical method for Sacubitril Calcium uses reversed-phase HPLC to separate the main compound from multiple related impurities. The described method uses an octadecylsilane column, methanol-based mobile-phase conditions and UV detection, demonstrating the importance of chromatographic impurity control for this material.
Commercial pharmaceutical/reference sources report ≥98% HPLC purity, while some pharmaceutical-intermediate manufacturers publish specifications of ≥99.0% HPLC assay. These values should be treated as commercial specifications rather than universal pharmacopoeial limits because I could not verify a current USP/BP/Ph. Eur. monograph establishing a universal Sacubitril Calcium API release specification.
A quality-focused Sacubitril Calcium manufacturing program should control raw materials, reaction conditions, stereochemical integrity, impurity formation, solvent residues, drying conditions and final product characteristics. Analytical testing should be performed using validated methods suitable for the intended pharmaceutical application.
For commercial pharmaceutical manufacturing, technical documentation may include batch-specific Certificates of Analysis, specifications, analytical reports, safety documentation, residual-solvent information and stability-related data where applicable.
Commercial sources describe Sacubitril Calcium as a powder or crystalline solid. Reference suppliers commonly recommend desiccated storage or storage around −20°C, while some pharmaceutical-intermediate manufacturers specify cool, dry and light-protected storage. Because storage requirements can depend on the particular solid form and validated stability data, the final commercial storage condition should follow the manufacturer's approved specification and stability program.
The material should be protected from excessive moisture, contamination and unsuitable temperature conditions and should be maintained in tightly closed pharmaceutical packaging.
Typical documentation for Sacubitril Calcium may include:
Sacubitril Calcium is an important specialized pharmaceutical intermediate associated with the manufacture of sacubitril-based cardiovascular drug substances. Its defined stereochemistry, calcium-salt form and established chromatographic impurity-control methods make consistent quality and analytical characterization important for pharmaceutical manufacturing.
For commercial pharmaceutical use, specifications should be established according to the intended process, applicable regulatory requirements and validated analytical procedures rather than relying on generic research-grade specifications.
| 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% |
| Heavy Metals | NMT 10 ppm |
| Melting Point | >140°C (decomp.) |