Despite the concern for safe processes, one of the most chemically benign separation processes has not been available to the drug industry.
Now Virginia Tech researchers with support from Procter & Gamble Pharmaceuticals have made a discovery that may allow a green-chemistry technique known as supercritical fluid chromatography (SFC) to be used in drug development.
The research will be presented at the 229th American Chemical Society national meeting in San Diego on March 13-17.
Drugs must be water-soluble in order to be useful in the body, meaning they are polar, or have some degree of charge. SFC uses carbon dioxide-based fluids for the isolation of compounds. Carbon dioxide is not polar, so could not be used to separate polar drugs, or ionic analytes.
"We discovered you can add a small amount of polar solvent that contains an ionic component that will allow carbon dioxide to separate ionic analytes," said Virginia Tech chemistry professor Larry Taylor. "It opens up an area of drug development to the use of nonpolluting carbon dioxide."
Jun (Sally) Zheng of Wuhan, China, a graduate student in chemistry at Virginia Tech, Taylor, and J. David Pinkston of Procter & Gamble Pharmaceuticals Health Care Research Center in Mason, Ohio, will present the poster, "Supercritical fluid chromatography of ionic analytes (MEDI 569)," from 6 to 8 p.m. Wednesday, March 16, as part of the Division of Medicinal Chemistry presentations.
Taylor and other students have been working with Pinkston for three years. Zheng recently joined the team and is studying how the additive allows the experiment to be successful. The company is providing her with a fellowship for spring and summer 2005.
For more information, contact Larry Taylor at (540) 231-6680 or ltaylor@vt.edu.
Poster abstract:
Addition of a small amount of polar solvent (e.g. modifier) which contains an ionic component (e.g. additive) to a CO mobile phase has shown major improvement in the elution of ionic analytes via packed column SFC. The study initially focused on the elution of sodium dodecylbenzene sulfonate. The additives studied were alkylammonium acetates. Conventional and Deltabond cyanopropyl and bare silica were the stationary phases. The effect of additive type and concentration on retention were investigated. Sodium 4- octylbenzenesulfonate and sodium p-toluenesulfonate also were studied. The study then turned to the use of sodium alkylsulfonates as mobile phase additives to elute ammonium salts. Propranolol hydrochloride and benzyltrimethylammonium- and cetylpyridinium-chloride were successfully eluted from the Deltabond phase after five minutes with a sulfonate additive. To gain insight into the elution mechanism(s), solid state NMR of the silica stationary phase has been performed. Modification of the stationary phase and ion pairing with the analyte are two possible elution mechanisms being considered.