Sulfanilamide is a synthetic sulfonamide antibacterial active pharmaceutical ingredient (API). It is chemically known as 4-aminobenzenesulfonamide and has the molecular formula C₆H₈N₂O₂S, molecular weight 172.20 g/mol, and CAS Number 63-74-1. The current BP 2025/Ph. Eur. monograph identifies Sulfanilamide as a sulfonamide antibacterial and specifies its quality on a dried-substance basis.
Sulfанilamide was one of the earliest clinically important sulfonamide antibacterial compounds. It acts by interfering with bacterial folate synthesis and has historically been used in pharmaceutical antibacterial preparations.
Sulfanilamide is structurally characterized by a p-aminobenzenesulfonamide moiety. It belongs to the sulfonamide class and serves as an important reference compound for related sulfonamide antibacterial substances.
The BP 2025 monograph describes Sulfanilamide as white or yellowish-white crystals or fine powder. It is slightly soluble in water, freely soluble in acetone, sparingly soluble in ethanol (96%), and practically insoluble in methylene chloride.
Sulfanilamide has the molecular formula C₆H₈N₂O₂S and molecular weight 172.2 g/mol. Its pharmacopoeial chemical designation is 4-aminobenzenesulfonamide. PubChem identifies the substance under CAS 63-74-1 and provides its chemical structure and associated substance information.
The API should be distinguished from Sulfanilamide Hydrochloride, which is a separate salt having CAS 6101-31-1 and a different molecular formula.
Sulfanilamide has historically been used as an antibacterial sulfonamide. Its pharmaceutical relevance also extends to its role as a structural and analytical reference compound for sulfonamide-related substances.
Modern use depends on the applicable pharmaceutical formulation and regulatory jurisdiction. Manufacturers should therefore evaluate the current approved application and applicable regulatory requirements before incorporating the API into a finished medicinal product.
Sulfanilamide is structurally similar to para-aminobenzoic acid (PABA). It competitively interferes with bacterial dihydropteroate synthase, an enzyme involved in folate biosynthesis.
Inhibition of this pathway reduces the formation of folate derivatives required for bacterial nucleic-acid synthesis, thereby inhibiting the growth of susceptible microorganisms.
Sulfanilamide has a current BP 2025 / Ph. Eur. monograph 1571, allowing considerably more precise CMS specifications than many older sulfonamide APIs. The monograph requires 99.0%–101.0% of 4-aminobenzenesulfonamide, calculated with reference to the dried substance.
The monograph specifies loss on drying NMT 0.5% and sulfated ash NMT 0.1%. Related substances are controlled chromatographically, with the unspecified impurity criterion at NMT 0.5% and the applicable overall impurity requirements defined in the monograph.
Sulfanilamide API manufacturing involves controlled chemical synthesis, purification, crystallization and drying. Manufacturing controls should ensure consistent identity, assay, related-substance profile and physical characteristics.
Validated analytical procedures are used to monitor the API throughout production and at final release. Process-related impurities and degradation-related substances should be controlled according to the applicable pharmacopoeial and regulatory specification.
Sulfanilamide is a crystalline solid. The BP 2025 identification procedure specifies a melting-point range of 164.5–166.0°C. The same monograph describes the substance as slightly soluble in water, freely soluble in acetone and sparingly soluble in ethanol (96%).
Sulfanilamide should be stored in appropriate pharmaceutical-grade packaging under conditions that protect the API from environmental exposure. The BP/Ph. Eur. monograph specifically states store protected from light.
Typical API documentation may include a Certificate of Analysis (CoA), specification sheet, Safety Data Sheet (SDS), batch analytical documentation, impurity profile, residual-solvent information and applicable regulatory documentation.
A qualified Sulfanilamide API manufacturer should maintain validated manufacturing and analytical processes capable of consistently meeting applicable pharmacopoeial requirements. Important quality attributes include assay, related substances, loss on drying, sulfated ash, identity and physical characteristics.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 99.0–101.0% |
| Loss on Drying | NMT 0.5% |
| Total Impurities | NMT 0.5% |
| Melting Point | 164.5–166.0°C |