Selexipag is a synthetic small-molecule pharmaceutical active ingredient belonging to the prostacyclin receptor agonist class. It is a selective non-prostanoid IP receptor agonist developed for the treatment of pulmonary arterial hypertension (PAH). Selexipag is marketed internationally as the active ingredient in Uptravi and is designed to activate the prostacyclin IP receptor pathway without being a prostacyclin analogue itself.
Selexipag API is identified by CAS Number 475086-01-2 and has the molecular formula C26H32N4O4S with a molecular weight of 496.62 g/mol. It is described as a pale yellow crystalline powder and is practically insoluble in water. The EMA active-substance assessment identifies Selexipag as a new active substance and confirms its chemical structure through elemental analysis, infrared spectroscopy, NMR, mass spectrometry, UV spectroscopy and X-ray powder diffraction.
Selexipag is chemically named 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide. It is an achiral compound and exists in different crystalline forms. EMA identified three polymorphic forms, designated Forms I, II and III. Form I was the principal stable form observed in manufactured batches, while Forms II and III were monitored as part of active-substance quality control.
The solid-state characteristics of Selexipag are particularly important because polymorphism can influence pharmaceutical processing, stability and performance. Appropriate API manufacturing therefore requires control of the crystalline form in addition to conventional chemical purity and impurity testing.
Selexipag has a molecular weight of 496.62 g/mol and a pKa of approximately 2.6. Its solubility is strongly dependent on pH. The EMA assessment reports that Selexipag is insoluble in aqueous solutions at approximately pH 2–4, freely soluble at pH 8 and very soluble at pH 9–12. It is non-hygroscopic in the solid state.
The API is synthesized through a multi-step chemical process using defined starting materials and intermediates. The manufacturing process includes critical process controls and crystallization steps designed to control chemical impurities and the undesired polymorphic forms.
Selexipag is primarily used in the pharmaceutical management of pulmonary arterial hypertension. It selectively activates the prostacyclin IP receptor, resulting in increased intracellular cyclic AMP and contributing to pulmonary vascular smooth-muscle relaxation.
The EMA-approved application covers long-term treatment of adult patients with pulmonary arterial hypertension, including idiopathic and heritable PAH and PAH associated with connective-tissue disorders and certain congenital heart conditions. Selexipag may be used alone or in combination with other PAH therapies according to the applicable approved product information.
Selexipag API requires a comprehensive analytical program. EMA documentation identifies identity testing by IR and HPLC, assay by HPLC, related-substance testing by HPLC, residual-solvent analysis by GC, loss on drying, residue on ignition or sulfated ash, heavy-metal testing, particle-size characterization and applicable microbiological testing.
Because Selexipag has multiple crystal forms, X-ray powder diffraction is an important characterization technique for solid-state identity and polymorphic control. Stability studies have also demonstrated that Selexipag can undergo hydrolytic degradation under acidic and basic conditions and oxidative degradation under peroxide conditions.
Selexipag intended for pharmaceutical manufacturing should be supported by controlled analytical documentation covering identity, chemical purity, related substances, residual solvents, water or loss on drying, residue on ignition, solid-state form and other applicable quality attributes.
A complete API technical package can include a Certificate of Analysis, specification sheet, analytical methods, impurity profile, residual-solvent information, polymorphism data, particle-size information, stability data and applicable GMP documentation.
Selexipag is a non-hygroscopic crystalline API, but its stability profile should still be protected through appropriate pharmaceutical packaging. The EMA assessment describes the active substance being packaged in low-density polyethylene bags placed inside a high-density polyethylene drum. Long-term stability data supported a retest period of up to 48 months when stored below 25°C under the assessed conditions.
Pharmaceutical documentation for Selexipag may include Certificate of Analysis, analytical method information, impurity specifications, residual-solvent results, polymorphic-form characterization, particle-size data, stability information and regulatory or GMP documentation as applicable.
Selexipag is a well-characterized pharmaceutical API with an established regulatory quality framework and extensive active-substance characterization. Its controlled chemical purity, related substances, residual solvents, polymorphic form and stability profile make analytical consistency especially important for pharmaceutical manufacturing.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.10% |
| Individual Impurity | NMT 0.15% |
| Melting Point | 115°C |