Ertapenem Sodium (33-13-7) Physical and Chemical Properties
Ertapenem Sodium
Monosodium salt of ertapenem, a broad‑spectrum carbapenem antibiotic; typically supplied as a crystalline powder for API supply, formulation and analytical use in parenteral product development.
| CAS Number | 33-13-7 |
| Family | Carbapenems (sodium salt) |
| Typical Form | Powder or crystalline solid |
| Common Grades | BP, EP |
Ertapenem sodium is the monosodium salt of the carbapenem antibiotic ertapenem and belongs to the 1-beta-methyl carbapenem structural class. The empirical composition of the salt is \(\ce{C22H24N3NaO7S}\); the chemical structure contains a bicyclic beta-lactam/azabicyclic core fused to a substituted pyrrolidine and a para-carboxamidobenzoyl side chain linked by a thioether. Key polar functionality includes a carboxylate (present as the sodium carboxylate in the salt), multiple carbonyls (amide and ketone), a secondary alcohol, and several hydrogen-bond donors and acceptors associated with the amide and heterocyclic groups. The molecule possesses multiple defined stereocenters (six) that are critical to its biological activity.
As a sodium salt of a beta-lactam antibiotic, ertapenem sodium is strongly polar and readily ionizes in aqueous media to yield the anionic ertapenem species and a sodium counter-ion; this ionization markedly increases aqueous solubility relative to the free acid. The high topological polar surface area (TPSA) and counts of hydrogen-bond donors and acceptors indicate low passive membrane permeability and low intrinsic lipophilicity compared with neutral small molecules of similar molecular weight. Chemically, the beta-lactam ring is the primary reactive motif: it is susceptible to nucleophilic attack (hydrolysis) and enzymatic cleavage by beta-lactamases, although ertapenem exhibits resistance to hydrolysis by a broad subset of beta-lactamases, including many extended-spectrum enzymes. Beta-lactams in general are hydrolytically labile under strongly acidic or basic conditions and can undergo ring opening and subsequent decomposition.
Ertapenem sodium is an established parenteral antibacterial agent used clinically as the sodium salt for intravenous and intramuscular administration; the salt form is selected to optimize solution stability and handling in pharmaceutical formulations. Common commercial grades reported for this substance include: BP, EP.
Basic Physical Properties
The sodium salt form produces a zwitterionic/ion-pair behavior in solution: the molecule as supplied contains a sodium counter-ion associated with the carboxylate anion. Physicochemical parameters that inform formulation and analytical work include the following computed descriptors and counts (values reported exactly as determined):
- Molecular weight: \(497.5\ \mathrm{g}\,\mathrm{mol}^{-1}\).
- Exact mass / Monoisotopic mass: \(497.12326557\ \mathrm{Da}\).
- Topological polar surface area (TPSA): \(184\ \text{\AA}^2\).
- Heavy atom count: 34.
- Formal (net) charge: 0 (neutral overall salt form).
- Defined atom stereocenter count: 6.
- Complexity: 900.
- Hydrogen-bond donor count: 4.
- Hydrogen-bond acceptor count: 9.
- Rotatable bond count: 7.
These values indicate a large, highly polar antibiotic molecule with multiple polar functional groups and low intrinsic lipophilicity; such parameters are consistent with parenteral administration and confined distribution largely to extracellular fluids.
Solubility and Hydration
Ertapenem sodium is the water-soluble salt form of ertapenem and dissociates in aqueous media to the anionic drug and sodium ion. The sodium carboxylate dramatically increases aqueous solubility compared with the protonated acid. In practice this salt form is used to prepare aqueous injections and reconstituted solutions for parenteral dosing; solubility will depend on pH, ionic strength, and counter-ion content of the formulation. No specific, experimentally established numeric solubility or hydration-state value is available in the current data context.
Thermal Stability and Decomposition
No experimentally established value for thermal decomposition onset or explicit melting/boiling temperatures is available in the current data context. As with related beta-lactam antibiotics, degradation pathways of practical concern include hydrolytic opening of the beta-lactam ring, decarboxylation under extreme conditions, and oxidative or thermally driven side-chain breakdown; formulation and storage are typically designed to minimize exposure to heat and moisture to preserve potency.
Chemical Properties
Complex Formation and Coordination
The salt contains multiple Lewis-basic oxygens (carbonyls, carboxylate) and a thioether sulfur; the anionic carboxylate and proximal carbonyl groups can participate in coordination to metal cations in solution. In formulated aqueous systems the sodium counter-ion is the primary coordinating cation, but chelation or non-covalent association with divalent transition metals can occur and may accelerate degradation (e.g., metal-catalyzed hydrolysis or oxidation). From a formulation perspective, control of metal contaminants and selection of compatible excipients reduce potential metal-mediated reactivity.
Reactivity and Stability
Ertapenem sodium retains the reactive beta-lactam functionality that confers antibacterial activity and also governs much of its chemical reactivity. The recorded pharmacological description specifies that ertapenem is resistant to hydrolysis by a variety of beta-lactamases, including penicillinases, cephalosporinases and some extended-spectrum beta-lactamases; this resistance is a structural property of the carbapenem core and side-chain substitution. Chemically, the molecule is susceptible to nucleophilic attack at the beta-lactam carbonyl (hydrolysis under strongly acidic or basic conditions), and to degradation pathways common to complex beta-lactams (ring opening, epimerization at stereocenters under forcing conditions, and oxidation of sensitive side chains). Controlled pH, avoidance of nucleophilic impurities, and low-temperature storage are standard measures to improve shelf life.
Molecular Parameters
Molecular Weight and Composition
- Molecular formula: \(\ce{C22H24N3NaO7S}\).
- Molecular weight: \(497.5\ \mathrm{g}\,\mathrm{mol}^{-1}\).
- Exact mass (monoisotopic): \(497.12326557\ \mathrm{Da}\).
- Heavy atom count: 34.
- Defined stereocenters: 6.
These parameters reflect a relatively large, highly functionalized antibiotic molecule whose formulation considerations are dominated by polarity and stereochemical integrity.
LogP and Ionization State
No experimentally established value for partition coefficient (logP or logD) is available in the current data context. Qualitatively, the sodium salt is highly polar and will have a low logP; in aqueous solution the predominant form is the ionized carboxylate paired with \(\ce{Na+}\), producing high water solubility and low passive membrane permeability relative to neutral small molecules.
Identifiers and Synonyms
Registry Numbers and Codes
- CAS number: 33-13-7
- European Community (EC) number: 836-232-1
- KEGG ID: D04049
- NCI Thesaurus Code: C61753
- RXCUI: 353107
- InChI:
InChI=1S/C22H25N3O7S.Na/c1-9-16-15(10(2)26)20(28)25(16)17(22(31)32)18(9)33-13-7-14(23-8-13)19(27)24-12-5-3-4-11(6-12)21(29)30;/h3-6,9-10,13-16,23,26H,7-8H2,1-2H3,(H,24,27)(H,29,30)(H,31,32);/q;+1/p-1/t9-,10-,13+,14+,15-,16-;/m1./s1 - InChIKey:
ZXNAQFZBWUNWJM-HRXMHBOMSA-M - SMILES:
C[C@@H]1[C@@H]2[C@H](C(=O)N2C(=C1S[C@H]3C[C@H](NC3)C(=O)NC4=CC=CC(=C4)C(=O)[O-])C(=O)O)[C@@H](C)O.[Na+]
(Identifiers presented exactly as recorded; structural identifiers are provided as inline codes.)
Synonyms and Structural Names
Common synonyms and depositor-supplied names include: Ertapenem sodium; MK-0826; Ertapenem sodium salt; L-749345; Invanz; Ertapenem sodium (USAN). The computed IUPAC name is recorded as: sodium 3-[[(2S,4S)-4-[[(4R,5S,6S)-2-carboxy-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]sulfanyl]pyrrolidine-2-carbonyl]amino]benzoate.
Parent and component relationships: the active moiety is ertapenem (parent), with sodium as the counter-ion in the salt form.
Industrial and Commercial Applications
Use as Salt Form or Excipient
The sodium salt is the pharmaceutical form used to enable parenteral formulations: the counter-ion increases aqueous solubility and facilitates manufacturing of sterile injectable solutions or lyophilized products for reconstitution. The salt form also influences pH of reconstituted solutions and can affect compatibility with common parenteral excipients and diluents. In formulation development the sodium salt is selected to balance solubility, stability, and injectable tolerability.
Representative Use Cases
Ertapenem sodium is used therapeutically as a systemic antibacterial agent for parenteral treatment of intra-abdominal infections, community-acquired pneumonia, acute gynaecological infections, diabetic foot infections of the skin and soft tissue, and for prophylaxis of surgical site infection following elective colorectal surgery when indicated. Its broad-spectrum bactericidal activity and relative resistance to many beta-lactamases make it useful in hospital and clinical settings where intravenous therapy is required.
If a concise application summary beyond these clinical uses is required for non-clinical industrial selection, no additional specific commercial applications are available in the current data context; in practice selection for formulation and procurement is driven by the solubility, stability and pharmacokinetic requirements described above.
Safety and Handling Overview
Toxicological Considerations
Ertapenem sodium is an antibacterial agent with documented pharmacology and clinical toxicology. Sensitization and respiratory allergy are highlighted hazards for occupational exposure: the substance has been associated with respiratory sensitization risk (GHS code H334: may cause allergy or asthma symptoms or breathing difficulties if inhaled). Environmental toxicity codes indicate high acute toxicity to aquatic life (H400) and long-term aquatic hazards (H411). Other clinical considerations include potential for alteration of normal flora and rare hypersensitivity reactions typical of beta-lactams; limited data indicate low passage into breastmilk at concentrations not expected to cause adverse effects in most breastfed infants.
Precautionary guidance included with hazard annotations recommends minimizing inhalation and environmental release, using appropriate respiratory protection for dusts/aerosols, and preventing contamination of aquatic environments. For detailed toxicological endpoints, dosage-related effects, and clinical contraindications consult product-specific toxicology documentation or regulatory labeling.
Storage and Handling Guidelines
General precautions for handling potent antibiotic powders and salts apply: minimize dust generation, avoid inhalation and skin contact, use appropriate engineering controls (local exhaust, containment for powders), and employ personal protective equipment (gloves, eye protection, respiratory protection when airborne dust is possible). Given the respiratory sensitization hazard, personnel with known beta-lactam allergy should avoid handling.
Store the material in a controlled environment to limit exposure to moisture and extremes of temperature and pH that accelerate beta-lactam degradation; packaging should prevent ingress of water and contamination by metal ions or nucleophiles. For detailed hazard, transport and regulatory information, users should refer to the product-specific Safety Data Sheet (SDS) and local legislation.
