The term ‘metal scavengers’ might call up images of strolling along a sunny beach, metal detector in hand, hunting for gold among glittering grains of sand.

But in the context of chemistry, the “beach” is a drug and the “metal detectors” are silica gels.

Metal scavengers are functionalized silica gels designed to react and bind excess metal complexes. They are essential to public health.

Identifying the Source of Metal Contaminants

In recent years, the short timeframe for quickly bringing drug candidates to market has increased the number of transition metal-catalyzed reactions being transferred from lead optimization to early scale-up. Although cross-coupling reactions have revolutionized modern synthetic chemistry and pharmaceutical synthesis, these processes can leave behind dangerous metal residue. Metal can enter into pharmaceutical substances or drug products from sources like metal catalysts and metal reagents used during synthesis.

Corollary trace metals are hazardous for human health and potential future synthetic steps. Most metals with top catalytic activities are also classified as Class 1 Metals (Pd, Pt, Rh, Ru, Ni, Os, Cr…), as stated by the ICH (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use). Class 1 Metals are known as “metals of significant safety concern”—those with the highest toxicity, including known or suspected human carcinogens, or possible causative agents of significant toxicity. Thus, removing post-reaction metal residues has become a major issue in the pharmaceutical industry.

Options for Removing Metals
Purifying APIs from residual metal catalysts via traditional methods, such as chromatography or distillation often leads to problems such as high costs, lost time, inefficiency, and reduced API yields.

Traditional purification methods are good – but not ideal – because:

  • Crystallization exposes a compound to high temperatures for a long period of time, increasing the risk of thermal degradation. Additionally, it is expensive, and total recovery is hard to achieve.
  • Solvent Extraction is a long process, requiring large volumes of solvents and often colored and viscous extracts. It is difficult (and in many cases, impossible) to optimize.
  • Chromatography is effective but also very expensive. It consumes large quantities of solvents (hence requiring further downstream processing) and is poorly suited to large-scale operations. It also typically reduces yields of an API or drug product.

What Metal Scavengers Do for You

Silica-based metal scavengers have been proven to be the most effective method for removing metal without contaminating drug candidates.

A silica matrix offers many advantages over polymers:

  • no swelling
  • more general solvent compatibility
  • higher mechanical and thermal stabilities
  • easily scalable applications
  • availability in different product formats, such as bulk, E-PAK flow cartridges, SPE or flash cartridges, etc.

Metal scavengers have transformed the field. They are benign because of their harsh mechanical stability and their resistance to minimal forms of leaching or swelling. A majority of the scavengers at SiliCycle are stable in all solvents – organic and aqueous – on a large pH/temperature scale, and also have an extended shelf-life. Due to their benign nature, they suit all R&D and manufacturing stages, and can be introduced at any time in your process.

How Metal Scavengers Work

What makes metal scavengers so easy to use is their heterogeneous nature. When used in bulk in a contaminated solution, all you need to do is filter off the scavenger with the bound metal and dispose of them.

When used in SPE or flash cartridges for batch reactions, the filtration process – with adapted experimental conditions – will leave the contaminant metal in the cartridge, rendering the solution metal-free.


The latest technology in scavengers is the E-PAK cartridge . It provides the same benefits as the SPE or flash, but for fixed bed/continuous reactions. E-PAK also features linear scalability - from the lab to commercial manufacturing processes.


Related Links                                                       

E-PAK® - Fixed Bed Flow-Through Purification Cartridges
E-PAK is a family of radial flow adsorption cartridges developed specifically for pharmaceutical processing. Offered with a choice of metal scavengers, bare silica & activated carbons, these cartridges are designed to remove precious metal catalysts, reaction-by-products or color from synthetic reaction mixtures and natural products.

SiliaMetS Metal Scavengers Portfolio

SiliCycle has the largest portfolio of grafted scavengers on the market, along with the largest spectrum of functionalities. Learn more about our extensive product line.

SiliaMetS Metal Scavengers Case Studies

SiliCycle Metal Scavengers are being used by a broad range of pharmaceutical companies – from lab to production scales. Here are some success stories highlighting the ease of use and reliable performance of our metal scavengers.

Confidential metal scavenging screening service

Take advantage of SiliCycle's expertise in metal removing capabilities! Let our R&D team quickly determine the optimal conditions for your pharmaceutical or manufacturing application.

Video: Metal Scavenging using SiliaMetS bulk functionalized silica

Video: SiliCycle SiliaMetS E-PAK Lab Scale Operation Tutorial