Protionamide, also known as Prothionamide, is a thioamide derivative used as an antitubercular active pharmaceutical ingredient. It belongs to the class of drugs used in tuberculosis treatment and is particularly associated with multidrug-resistant tuberculosis treatment regimens.
Protionamide has the molecular formula C₉H₁₂N₂S, molecular weight 180.27 g/mol, and CAS number 14222-60-7. Its IUPAC name is 2-propylpyridine-4-carbothioamide.
Protionamide is a pyridine carboxamide/thioamide derivative. Its antitubercular activity is associated with inhibition of mycolic-acid biosynthesis after metabolic activation, contributing to disruption of the mycobacterial cell wall.
The International Pharmacopoeia describes Protionamide as yellow crystals or a crystalline powder, practically insoluble in water and soluble in dehydrated ethanol, methanol and acetone. It should be kept in a tightly closed container and protected from light.
| Parameter | Details |
|---|---|
| Product Name | Protionamide |
| Synonym | Prothionamide |
| CAS Number | 14222-60-7 |
| Molecular Formula | C₉H₁₂N₂S |
| Molecular Weight | 180.27 g/mol |
| IUPAC Name | 2-Propylpyridine-4-carbothioamide |
| Chemical Class | Pyridine thioamide |
| Therapeutic Class | Antitubercular |
| Category | Active Pharmaceutical Ingredient |
| Appearance | Yellow crystals or crystalline powder |
| Water Solubility | Practically insoluble |
| Ethanol | Soluble |
| Methanol | Soluble |
| Acetone | Soluble |
| Storage | Tightly closed container, protected from light |
| Pharmacopoeial Reference | The International Pharmacopoeia |
Protionamide is an antitubercular drug used in tuberculosis treatment. It has particular relevance in treatment regimens for drug-resistant tuberculosis and has been evaluated for multidrug-resistant TB.
Its pharmacological action is related to inhibition of InhA, an enzyme involved in mycolic-acid synthesis, after conversion to an active metabolite. Interference with mycolic-acid production compromises the integrity of the mycobacterial cell wall.
Protionamide has an official International Pharmacopoeia monograph. The 2025 Twelfth Edition specifies the substance to contain 99.0–101.0% of C₉H₁₂N₂S, calculated with reference to the dried substance.
The pharmacopoeial identity tests include IR spectroscopy, UV absorption and HPLC retention-time comparison. The monograph also specifies heavy metals, sulfated ash, loss on drying, acidity and related substances.
The International Pharmacopoeia specifies heavy metals NMT 20 μg/g (20 ppm), sulfated ash NMT 1.0 mg/g (0.10%), and loss on drying NMT 5.0 mg/g (0.5%).
For related substances, the pharmacopoeial HPLC procedure uses the principal Protionamide peak as the reference: an individual impurity is limited to approximately 0.5%, while the sum of impurity peaks is limited to approximately 1.0%.
Protionamide API manufacturing requires control of chemical identity, assay, related substances, moisture, inorganic residue and elemental impurities.
The International Pharmacopoeia uses HPLC with UV detection at approximately 290 nm for the related-substances and assay procedures. The chromatographic system also evaluates separation between Protionamide and Ethionamide, with the monograph requiring adequate resolution between the corresponding peaks.
Quality control may therefore include:
Protionamide should be stored in a tightly closed container and protected from light. The International Pharmacopoeia specifically identifies these storage requirements and notes that Protionamide may exhibit polymorphism.
Recommended CMS wording:
Store in tightly closed, light-protective containers under controlled pharmaceutical storage conditions. Protect from excessive heat, moisture and light.
Typical Protionamide API documentation may include:
Protionamide has a defined International Pharmacopoeia quality standard, allowing its API quality to be evaluated against established numerical requirements. The key pharmacopoeial controls include 99.0–101.0% assay, NMT 0.5% loss on drying, NMT 0.10% sulfated ash, NMT 20 ppm heavy metals, NMT 0.5% individual impurity and NMT 1.0% total related substances.
| 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% |
| Residue on Ignition | NMT 0.1% |
| Heavy Metals | NMT 20 ppm |
| Individual Impurity | NMT 0.10% |
| Total Impurities | NMT 1.0% |