Flash and MPLC Chromatography
Flash and MPLC (Medium Pressure Liquid) Chromatography are fast and economic liquid chromatographic methods used mainly in the 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 yiel and selectivity special adsorbents are available. Both pre-packed flash columns and bulk media for glass columns are available. TLC is frequently used as a pre-test for flash chromatography development. Important is 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 chemistry in Industry and Universities because it 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 since many years. 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
The single compound purifier may start with a mixture of target products and a number by-products in the reaction broth. The aim may be to fractionate the compound mixture into single compounds, to analyse them individually for further analysis or to isolate the target compound in large quantities from to the 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 system with which they can purify the target compound in mg to gr quantities fast and to a fairly 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. The 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. The 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 people often are more closer to high trough put systems. The elder generation has lots of practical experience and they use all their senses in their work. 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 and there are also companies where purchasing personel desided to procure only one type of system from one supplier because they were able to 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 efficientr 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. The large international equipment companies sold the large pharmaceutical companies the idea that with fully intergrated and automated turn key system will enable them to purify thousands of samples with minimum amount of labor ond to obtain wide range of compound data to accellerate speed to the market. Many signed up with one supplier and by doing that financed the supplier company the path into automation. Hundred of thousands of Euro/USD in old systems were removed and given away to School or Universities in Africa and replace with millions in new automated system. The shock came soon when most companies realised that the the large masses of samples did not realise and that complexity of system required new forms of 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 system. 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 budget, 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 lergerage 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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Overthe 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 smaler blocks/teams that are separted 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 though to increase producttivity through competition. Research and innovation is serendipty. Productivity cant 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 tothe 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 ireplaceable 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 paralell 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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Purification of organic synthesis products