Flash and Medium Pressure LC
Most compounds come in mixtures or are contaminated with metabolites and by-products. Some can be separated and purified by recrystallisation. Unfortunately this process is cumbersome and time consuming . Much easier and faster is to use Flash and Medium Pressure LC.
Flash and MPLC (Medium Pressure Liquid) Chromatography
Is a fast and very competitive liquid chromatographic methods. The method is used in sample preparation and preparative scale purification of organic and inorganic compounds and biologics.
The most commonly used stationary phase is silica gel (40-63μm particles for Flash and 20- 40 μm particle for MPLC).
To improve yield and selectivity special adsorbents are available. They can be purchased in pre-packed flash columns and as bulk media for packing glass columns and cartridges.
Thin Layer Chromatography (TLC) is frequently used as a pre-test in flash chromatography development.
Important is to know that the TLC plates are compatible with the particle in the column or pre column to assure reproducible transfer of TLC results to flash columns.
Flash it the most popular purification methods for synthetic chemists working in Industry and Universities.
Flash Chromatography is fast and easy to execute particularly for compounds that do not crystalize easily. Biochemist also use it for purification of natural compounds and bio molecules.
In the chromatographers community a wide range of purification process philosophies exists. The chromatographer community is divided ;
- The single compound purifier (Drug Discoverer, Optimizer, Scolars, Universities)
- The multi compound purifier ( Combinatorial Chemistry , High through put specialists)
The single vs. multiple compound purifier
As a rule of thumb synthetic chemistry produces mixtures of target compounds or almost target compounds and a number by-products. The chemists purpose may be to to fractionate the compound mixture into single compounds. To analyse them individually or to isolate the target compound in large quantities from by-products for further processing (Clinical investigation , next step synthesis etc.)
In most cases the purifier doesnt know the detailed chemistry of the compound mixture. He does however know the source of his sample and what he aims to achieve.
- Flash chromatographers and Medicinal Chemist perfer simple and competitive purification systems. They aim to purify the target compound in mg to gr quantities fairly quickly and at high high purity (90 to 95%). The compound is then dried and taken for further steps in synthesis or for structural elucidation.
- Combinatorial Chemist often deal with many different samples to be purified. They operate generally with micro well plates (e.g. 24 cavities with 0.5 to 3 ml capacity , 48 Micro well plate with 0.5 to 1.5 ml capacity or 98 micro well plate with 0.1 to 0.5 ml capacity.) They often use Analytical Chromatography equipment (LC-MS) in combination with short large diameter HPLC columns commonly refered to as “Combinatorial Chemistry Column” and special Software.
Which method is better? Both methods have their own weakness and strength. It depends very much on the users. Jounger generation are more closer to high-through-put systems. The elder generation has lots of practical experience. They prefer to work more focussed on single compounds.
Turn Key Systems vs. Self Assembled Systems
Over the years we created and sold many different systems for combinatorial, medicinal and natural compound purifiers. We often observed that in one and the same company different systems were installed.
Creating novel API is a creative process. There are few real theories available to design the novel molecules rationally.
Particularly in larger companies purchasing personel desided what to procure. The ofter sign contracts with one supplier because they often obtain quantity discounts.
After more than 30 years of trend observation we conclude that that there is no such thing as the most effective or efficient system. The key factor in productivity is the person that performs Flash or MPLC. In the nienties manager returned from conferences and technology exhibition whith the clear message that automation is the answer to productivity. International equipment companies sold to the large pharmaceutical companies the idea that fully intergrated and automated turn key system will empower their staff to purify thousands of samples with minimum amount of labor. Automated paralel Flash was the buzz word. A few years later the purchasing managers signed up with very few large US equipment companies that offered parallel combinatorial LC-Column with MS integration. In an effort to get LC-MS established in Pharma companies major MS manufacturere offered fully intergared LC-MS systems. Interestingly the pharmaceutical companies were suddenly ready to finance the system development. Many pharma companies signed up with one supplier. For most chromatographer wanted to test a number of equipment and to evaluate which one to offer the best choice. Purchasing personell quickly started to offer the traditional equipment to Schools or Universities in Africa and so forcing the chromatographers to use what they have been given. The transition was anything else but smooth because the users wer hardly ask what they require. The shock came soon when most companies realised that the predicte productivity was not reached. Manager soon realised that 1. availability of primary raw materials was insufficient. 2. Diversity and reproducibility ofseparation material was a problem and 3. Complexity of the new system also required new forms of application labour.
A few years later we wer called by the chemist to dicuss manual system. It was interesting to observe the chromatographers. All wanted to buy specialty pumps and systems. We were often told that they are regarded as specialist and so it was important that their equipment also had to appear as unique and high quality performing tool.
Over the years we observed that those labs which had a clear budgets, agreed performance data and freedom to choose their own purchases, were the most motivated and productive labs. Competition in those labs was high and so the individual technician or chemist communicated intensly with outside suppliers to increase his personal knowledge. Soon the IPR people demanded that contact with outside suppliers to be stopped. They asserted that external suppliers are potential thiefs of know how. The created fear spread into many departments and outside to Venture Capitalist. Amongst top management grew the idea to outsource the high risk elements in the drug development chain to Universities. Venture capitalist saw a business model emerging that promissed huge gains for the VCs. They were able to pick up say 20 Mio from a researching Pharma company and to leveragage it to say 100 Mio through institutional investors. They then contacted interested PhD active in a particular filed of research and offered them to finance their research and to form with them a company that was able to sell the research to the investors and to the market. The offer was very atractive because the only thing to do was to sign their Term Sheets in which they demanded clinical phase one to be completet in one or two years. Productivity gains of this development is well researched and explained in the EROOM Graph. Unfortunately, it is a tabooe to talk about the damage caused by managers that have take the human element out of the calculation and just make short term finance beased decisions. Until about turn of the century a number if private companies created new and improved flash and MPLC systems and helpt their clients to use them efectively and efficiently. Now those companies have disappeared and very few new companies emerged in the new economies.
We continue to supply high quality eqipment and systems because we have discovered new application is new market. We cater for buyders that want to create their own individual systems or for buyer that require turn key systems. We also help with advice to create system the perform exelently to a partiucular specification . Furthermore we offer a wide range of consumable products to maximize yield and purity for a particular group of compounds.
We also represent innovative companies that create new tool and strategies.
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If you are new in the field of compound purification we recommend to visit the Prep and Process section to familiarize yourselves with the variables to be addressed in this field. Please click here
Fundamentals in Prep and Process Chromatography
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Over the years we also observed managed trends dictated by the lab or divisional head. With change of top management often new philosophies or methods are being introduced in a working place. This leads often to disruption and fear amongst people that have grown into a routine. Conversion to a new method is often slow because people have to get used to the new routine. In the pharmaceutical industry often assembles groups of specialist in smaller blocks/teams that are separated by locations (Group X in Lab Y or location Z vs Group A in Lab B and location C). Top management uses such strategies with the thought to increase productivity through competition. Research and innovation is serendipity. Productivity can’t be improved this way. Over the past 50 years the most innovative companies/groups are those that communicate job security for those groups that produce new to the world concepts for a clearly communicated target market and the freedom to work together with innovative suppliers and new tools but not convenience or champion creating tools. (Many technical people love to buy/use complex tools to imply that they special people competent and irreplaceable individuals.)
We supply competitive and easy to use MPLC pumps combined with pack cartridges and glass columns for manual operations.
We also offer high through-put parallel Flash und MPLC systems controlled be complex software for large scale purification of natural or synthetic products.
We offer 30 years of experience as developers of unique sample preparation processes and materials.
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