Influence of mobile phase composition on the preparative separation of profens by chiral liquid chromatography
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abstract
Liquid chiral chromatography of ketoprofen and flurbiprofen enantiomers is carried out using an amylose-based stationary phase. The mobile phases used for profens chiral separations are usually a hydrocarbon-alcohol combination, with high hydrocarbon content. However, profens show poor solubilities in hydrocarbon solvents when compared to alcohols. When the final objective is high productivity preparative separations, besides retention time, selectivity and column efficiency, solubility of the racemic drug is always a mandatory aspect to take into account. This work shows that an increase of the alcoholic content in the mobile phase is possible without a decrease in selectivity and column efficiency. Considering the chiral separation of ketoprofen and flurbiprofen enantiomers, results show that the mobile phase needs only a small quantity of acidic modifier and can be composed by a high or even pure alcoholic content. Additionally, it is found that the type of alcohol to be used can differ, depending on the profen racemic mixture to be separated.
The chirality of drugs is an important issue for the pharmaceutical industry, since the different
enantiomers of a racemic drug may have distinct pharmacological activities, pharmacokinetic and
pharmacodynamic effects. Because of its chiral selectivity, human body reacts with a racemic drug
differently, and metabolise each enantiomer on separate pathways producing different
pharmacological activity. Thus, one isomer may produce the desired therapeutic activities, while the
other may be inactive or even, in worst cases, produce unwanted effects.
The chirality of drugs is an important issue for the pharmaceutical industry, since the different
enantiomers of a racemic drug may have distinct pharmacological activities, pharmacokinetic and
pharmacodynamic effects. Because of its chiral selectivity, human body reacts with a racemic drug
differently, and metabolise each enantiomer on separate pathways producing different
pharmacological activity. Thus, one isomer may produce the desired therapeutic activities, while the
other may be inactive or even, in worst cases, produce unwanted effects.
Flurbiprofen [2-(2-fluoroo4-biphenyl)-propionic acid] and ketoprofen [2-(3-benzoylphenyl)-propionic
acid] belong to a family of chemicals named 2-arylpropionic acids, or profens, an important sub-class
of the frequently prescribed and used drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). A
considerable number of these drugs possess antipyretic activity in addition to its analgesic and antiinflammatory
actions, and thus have utility in the treatment of fever. The main primary indications for
NSAIDs therapy include rheumatoid arthritis, osteoarthritis, acute gouty arthritis, ankylosing
spondylitis and dysmenorrhea (DeRuiter, 2002). The importance of this class of drugs is supported by
U,e fact that, in the last twenty years, drugs like aspirin, phenazone derivatives or acetaminophen are
being supplemented by profens (Brune and Hinz, 1998).
