Penicillin G, also known as benzylpenicillin, is a classical β-lactam antibiotic belonging to the penicillin family. It is an antibacterial active pharmaceutical ingredient used in the development and manufacture of pharmaceutical formulations intended for the treatment of susceptible bacterial infections. Penicillin G acts by interfering with bacterial cell-wall synthesis through binding to penicillin-binding proteins, ultimately causing inhibition of peptidoglycan cross-linking and bacterial cell lysis.
For pharmaceutical applications, Penicillin G is commonly handled as a salt, particularly Penicillin G Sodium (benzylpenicillin sodium) and Penicillin G Potassium (benzylpenicillin potassium). These salts improve the pharmaceutical handling and formulation characteristics of the benzylpenicillin active moiety. The sodium salt has CAS No. 69-57-8, molecular formula C16H17N2NaO4S, and molecular weight 356.37 g/mol, while the potassium salt has CAS No. 113-98-4, molecular formula C16H17KN2O4S, and molecular weight 372.48 g/mol.
The free-acid form of Penicillin G has CAS No. 61-33-6, molecular formula C16H18N2O4S, and molecular weight 334.40 g/mol. It is also known as benzylpenicillin or benzylpenicillinic acid.
Penicillin G Potassium is a monopotassium salt of benzylpenicillin and is recognized in the USP-NF with the molecular formula C16H17KN2O4S and molecular weight 372.48 g/mol. The USP monograph specifies a potency of 1440–1680 Penicillin G Units/mg.
Penicillin G Sodium is the monosodium salt of benzylpenicillin. The USP monograph specifies a potency of 1500–1750 Penicillin G Units/mg.
Penicillin G APIs are important materials for pharmaceutical manufacturing, particularly for formulations based on benzylpenicillin. Depending on the intended formulation and route of administration, manufacturers may select the sodium or potassium salt. Penicillin G potassium and sodium are especially relevant to parenteral pharmaceutical products.
The USP recognizes dedicated monographs for Penicillin G Potassium and Penicillin G Sodium. This makes it important to identify the exact salt form when preparing API specifications, certificates of analysis, regulatory documentation, and product listings.
The USP monograph for Penicillin G Potassium establishes potency at NLT 1440 and NMT 1680 Penicillin G Units/mg. USP analytical requirements include spectroscopic identification, chromatographic comparison of the major peak, crystallinity, pH, loss on drying, bacterial endotoxins where applicable, and sterility when the material is labeled sterile. The USP pH requirement is 5.0–7.5, while loss on drying is NMT 1.5%.
The USP assay is expressed as Penicillin G Units/mg rather than a conventional percentage HPLC assay. Therefore, CMS content should not incorrectly describe the USP potency requirement as “Assay by HPLC 98–102%.” The chromatographic procedure is used to determine potency in biological units per milligram.
Penicillin G is a β-lactam compound and requires controlled pharmaceutical handling. API quality assessment can include identity, potency, chromatographic purity, pH, moisture or loss on drying, crystallinity, endotoxin and microbiological attributes according to the applicable grade and intended use.
For a Penicillin G product page, the exact salt should always be specified. Penicillin G, Penicillin G Sodium, Penicillin G Potassium, Penicillin G Benzathine, and Penicillin G Procaine are not interchangeable API entries because they have different molecular weights, CAS numbers and specifications.
Penicillin G remains an important reference compound within the penicillin antibiotic class. Its established pharmaceutical history, recognized pharmacopoeial standards and well-defined potency testing make it relevant for pharmaceutical API manufacturing and formulation development.
For commercial and regulatory documentation, manufacturers should specify the exact form, pharmacopoeial standard, potency basis, packaging conditions and analytical specifications applicable to the supplied material. The USP monographs provide distinct specifications for Penicillin G Sodium and Penicillin G Potassium.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.5% |
| Residue on Ignition | NMT 0.5% |
| pH (1% Solution) | 5.0–7.5 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | ≤ 1.5% |