In the fast-paced world of drug discovery, every day counts—and so does every drop of solvent. Yet for chemists working with polar, unstable prodrugs and new chemical entities (NCEs), one critical step has remained frustratingly slow, expensive, and inefficient: purification.
The conventional go-to method, preparative HPLC, is powerful but far from perfect. It demands large volumes of costly solvents, long processing times, and expensive equipment. Worse, many polar or labile compounds degrade under the harsh acidic or basic conditions typically used in HPLC, compromising yield and purity. For early-stage discovery teams, this creates a persistent bottleneck that slows down projects and inflates costs.
But what if there were a simpler way?
A Practical Breakthrough from Syngene’s Discovery Team
This is exactly the challenge that Syngene’s Discovery Chemistry team set out to solve. Driven by real-world obstacles faced in the lab, the team developed an elegant yet robust solution using C18 reverse-phase silica cartridges—a technique long used in analytical chemistry but rarely leveraged for full-scale purification of complex drug candidates.
Instead of running unstable compounds through harsh HPLC workflows, they adapted C18 solid-phase extraction cartridges for bench-top purification. The result? A method that’s not only faster, greener, and more economical, but also gentler on sensitive molecules.
The Impact: Faster Turnaround, Lower Costs, Higher Efficiency
The benefits of this method are compelling:
- Up to 97% reduction in solvent use compared to prep-HPLC
- Turnaround time reduced from 48 hours to as little as 1 hour
- Comparable or even higher purity and recovery for most compounds
- Minimal equipment investment, making it accessible to smaller labs and academic researchers
This simple innovation unlocks critical agility for medicinal chemists working under tight timelines and budgets. It’s not just about saving time and money—it’s about enabling faster decisions, protecting sensitive drug candidates, and keeping discovery programs on track.
In one case, a prodrug purified via prep-HPLC required 3,800 mL of solvent and took two full days. The same compound, purified with the C18 cartridge method, took just 140 mL of solvent and three hours—with virtually no loss in purity or recovery.
Photo: Syngene’s discovery chemistry team from left to right Dr. Umesh Mali, Balamurali Rajagopal, Dr. Venkataramasubramanian V., Santosh N. Patil, and Dr. Raja K. Rit.
A Solution with Global Relevance
By rethinking how we purify unstable and polar compounds, Syngene’s scientists are paving the way for a more agile and sustainable discovery process—not only within their own labs but potentially across the industry.
“This approach offers a practical and scalable alternative to prep-HPLC, especially for labs that cannot afford the infrastructure or time-intensive workflows,” said Dr. Santosh Patil. “It’s a small shift in method with a big impact on how we work.”
The team envisions this method as a valuable first-pass purification tool, even in industrial settings, helping extend the life of prep-HPLC columns and shrinking overall turnaround times.
Want to explore how Syngene’s integrated drug discovery solutions can accelerate your pipeline? click here.
Read the full paper-
Venkataramasubramanian, V., Motamarri, K. K., Rajagopal, B., Agarwal, V., Mali, U. W., Rit, R. K., Satish, P., Mohanty, S. K., & Patil, S. N. (2025). A simple and efficient approach to overcome the purification bottleneck of polar unstable prodrugs & new chemical entities (NCEs). Journal of Chromatography B, 1257, 124588. https://doi.org/10.1016/j.jchromb.2025.124588
