Piperaquine is a synthetic antimalarial active pharmaceutical ingredient belonging to the aminoquinoline class. It is a long-acting antimalarial compound that has been used in combination with artemisinin derivatives, particularly dihydroartemisinin, for the treatment of malaria.
Piperaquine has the molecular formula C₂₉H₃₂Cl₂N₆, a molecular weight of 535.5 g/mol, and CAS Number 4085-31-8. Its chemical structure contains two 7-chloroquinoline groups linked through piperazine and propyl groups.
Piperaquine is an aminoquinoline antimalarial with a long duration of action. It was developed in China in the 1960s and subsequently became an important component of combination antimalarial therapy. Piperaquine is commonly used together with an artemisinin derivative rather than as a modern standalone antimalarial.
The pharmaceutical form widely used for formulation is Piperaquine Phosphate, specifically Piperaquine Tetraphosphate Tetrahydrate. This salt contains four phosphoric acid equivalents and four waters of hydration and has the molecular formula C₂₉H₅₂Cl₂N₆O₂₀P₄ with a molecular weight of 927.5 g/mol.
Piperaquine is primarily associated with antimalarial pharmaceutical formulations. Its major pharmaceutical application is in combination therapy with an artemisinin derivative.
Applications include:
Piperaquine is included in combination products such as dihydroartemisinin/piperaquine, which are used in malaria treatment.
For API manufacturing, identity, assay, related substances, water content, residual solvents and other quality attributes should be controlled according to the applicable approved specification.
Published analytical research has demonstrated validated HPLC methods for determining piperaquine phosphate and its degradation products. One stability study used piperaquine phosphate reference material with purity >99.0% for analytical work.
Commercial reference material is also available with a stated purity of >98.0% by HPLC, but this should not be represented as a pharmacopoeial release limit unless the applicable monograph specifies it.
Piperaquine API intended for pharmaceutical applications should be manufactured under appropriate pharmaceutical quality systems and tested using validated analytical procedures.
For Piperaquine Phosphate, quality control may include:
The exact limits should correspond to the API form and the current approved specification.
| 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% |
| Residue on Ignition | NMT 0.1% |
| Individual Impurity | NMT 0.5% |
| Water Content | NMT 0.5% |
| Melting Point | 193–204°C (decomposes) |