Separation of profens enantiomers

What is it about?

The chromatographic retention and separation of the enantiomers of drugs including flurbiprofen, ibuprofen, ketoprofen, indoprofen, and fenoprofen were studied by using a high-performance liquid chromatography with 5 new chiral stationary phases. Sorbents based on silica gel (Kromasil KR100-7-SIL (Akzo Nobel, Sweden) had grafted macrocyclic glycopeptide antibiotics, including oritavancin (O-CSP), eremomycin (E-CSP) and its derivatives chloreremomycin (Chloro-E-CSP), amido-eremomycin (Amide-E-CSP), adamantylamido-eremomycin (Adamantylamide-E-CSP) were used as chiral stationary phases (CSP). Comparison of sorbents was carried out using 100% methanol with the addition of triethylammonium acetate as an eluent. The obtained enantioselectivity of profen separation decreased in the series O-CSP>Chloro-E-CSP>Adamantylamide-E-CSP>E-CSP>Amide-ECSP. The highest resolution of chromatographic peaks (Rs > 2.0) was obtained by separating the enantiomers of flurbiprofen, indoprofen, and ketoprofen on sorbents with grafted oritavancin and chloreremomycin. The study discusses the mechanism for the chiral recognition of enantiomers of 2-phenylpropionic acid derivatives or profens by macrocyclic glycopeptide antibiotics structurally related to eremomycin. It was found that the carboxyl group in the eremomycin molecule plays an insignificant role in chiral recognition, since its conversion to the amide group (Amide-E-CSP sorbent) only slightly reduces enantioselectivity compared to ECSP. Change of the steric hindrance in the chiral recognition of profens by introduction of an adamantyl substituent into the amide group increases the enantioselectivity of the Adamantylamide-E-CSP sorbent with respect to E-CSP. The most pronounced effect on the enantioselectivity of chiral recognition for the studied sorbents caused a change in the structure of aromatic fragments of eremomycin. The introduction of a chlorine atom into the benzene ring (Chloro-E-CSP sorbent) and addition of pair-phenyl-pair-benzyl substituent (OCSP sorbent) provided the highest enantioselectivity for these sorbents among all studied CSP.

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Why is it important?

Profens reprent an important class of drugs, but only one enantiomer is usually active. So, it is important to have enantioselective stationary phases to detect enantiomeric purity of these drugs from different vendors.

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