Iodixanol Purification Case Study

1. Background

Among diagnostic CT imaging tools, contrast media create contrast by altering local tissue density, serving as core agents that enable physicians to accurately identify lesions. As a representative second-generation nonionic organic iodine contrast medium, iodixanol features high safety and a wide range of clinical applications, making it one of the most widely used contrast agents in domestic clinical practice.

In recent years, volume-based centralized procurement and accelerated domestic substitution have fueled rapid expansion of the iodixanol market. However, widespread price cuts have imposed substantial cost pressures on manufacturers. On one hand, injection-grade products must adhere to strict purity and safety thresholds; on the other hand, profit margins continue to shrink. Under this backdrop, purification processes have become a core determinant of product competitiveness.

2. Purification: A Critical Piece of the Puzzle

Industry data shows that China’s iodixanol injection market size grew from RMB 2.86 billion to RMB 4.32 billion between 2021 and 2025, representing a compound annual growth rate (CAGR) of 10.9%.

Driven by national centralized procurement and provincial alliance tenders, the average price of the 100mL:30 specification product dropped from RMB 280 to approximately RMB 110. Nevertheless, the "lower prices for higher sales volume" effect is prominent: total sales volume surged from 18.5 million bottles to 39.2 million bottles, while the domestic generic drug market share rose from less than 40% to 68%. Looking ahead to 2030, fueled by growing CT equipment penetration and population aging (the share of residents aged 60 and above will exceed 21%), the market size is projected to reach RMB 6.5–6.8 billion.

Behind the booming market, the purification and production of iodixanol active pharmaceutical ingredients (APIs) face three intertwined technical and cost challenges:

Difficult impurity separation: Ionic impurities, related substances and degradation products generated during synthesis feature molecular structures highly similar to iodixanol. Conventional separation methods fail to remove these impurities thoroughly, jeopardizing final product purity and medication safety.
Short service life of traditional packing materials: Iodixanol purification is carried out under high aqueous and weakly acidic/alkaline conditions. Traditional silica-based reversed-phase packing materials exhibit poor tolerance under such environments, requiring frequent replacement and continuously driving up consumable costs.
Strict cost control requirements: Price cuts under centralized procurement have squeezed corporate profit margins. Purification processes must meet higher standards for sample loading capacity, product yield and batch consistency, while complying with injection-grade quality specifications, low nephrotoxicity requirements and the economic demands of large-scale manufacturing.

Faced with dual pressures of centralized procurement price reductions and quality upgrades, manufacturers must balance superior contrast performance, low nephrotoxicity and favorable physicochemical properties of iodixanol with effective production cost control. The purification process stands out as a decisive factor in product quality and cost competitiveness.

3. Packing Material Introduction

Hand Science independently developed the Hedera PS reversed-phase polymeric packing material, delivering an optimized solution tailored to the purification demands of iodixanol and other organic iodine contrast media.

Manufactured with a polystyrene/divinylbenzene (PS/DVB) matrix, this packing material boasts high crosslinking density, large specific surface area, robust mechanical strength and uniform particle size distribution. It features low swelling rate in organic solvents and outstanding chemical stability, with a working pH range of 1–14. Resistant to corrosion and easy to regenerate, it tolerates 100% aqueous mobile phases and perfectly matches the operating environment of iodixanol purification processes.

When applied to iodixanol separation and purification, Hedera PS simultaneously delivers high loading capacity, superior separation efficiency, extended service life and low operating costs, making it particularly suitable for large-scale industrial production.

4. Purification Protocol

This purification validation adopted crude iodixanol samples sourced from actual production, with core control targets as follows: alkyl ether impurities < 0.4%, product yield > 90%.

Preparation Parameters

Equipment: Hanbon High Performance Liquid Chromatography System NP7000-NU3000
Packing Material: Hedera PS

Column Specification: DAC50mm, Loading Capacity: 110 g/L

Column Specification: DAC1600mm, Loading Capacity: 110 g/L

Comparison of Core Indicators Before and After Purification

Sample	Purity (%)
Crude Product	98.00
Final Purified Product	99.63

Experimental results demonstrate that under a sample loading concentration of 110 mg/mL, purification of crude iodixanol with Hedera PS elevates purity from 98.00% to 99.63%. The DAC column operating pressure remains stable below 2 MPa, fully satisfying quality standards and production process requirements.

5. Conclusion

Currently, Hedera PS packing materials are widely deployed for separation and purification across organic compounds, natural products, chemical drugs, antibiotics, peptides and proteins. Its integration into iodixanol purification workflows delivers multiple benefits: deep impurity removal, consistent batch-to-batch product quality and improved medication safety. Furthermore, its ultra-long service life and high loading capacity drastically reduce unit production consumption, equipping manufacturers with robust support for long-term cost control amid normalized centralized procurement.

The Expert Consensus on Clinical Application of Iodine Contrast Media designates iodixanol as a preferred contrast agent for patients with renal insufficiency, pointing to rigid and clear market demand in the future. For manufacturers, selecting the optimal purification packing material secures dual competitive advantages in both product quality and production costs.

Hedera PS – Empowering every bottle of high-quality iodixanol.