Enantiomer ibuprofen

Non steroidal antiinflammatory drugs were among the first classes of chiral compounds investigated in the early stages of the application of macrocyclic antibiotics as chiral selectors therefore, they were screened on vancomycin [7], teicoplanin [30], ristocetin A [33] CSPs under RPmode systems, and on avoparcin CSP under NP mode systems [37]. The enantioresolution of a variety of pro fens was later reported on commercially available vancomycin CSPs [128, 168], and recently on a ME-TAG CSP [58]. Ibuprofen enantiomers were also separated on a CDP-1-containing CSP [55]. Glycopeptide A-40,926 CSP was successfully employed in the analytical and semipreparative separation of 2-arylpropionic acids [63]. 

JC Reijenga, BA Ingelse, FM Everaerts. Thermodydnamics of chiral selectivity in capillary electrophoresis separation of ibuprofen enantiomers with (3-cyclodextrin. J Chromatogr A 792 371-378, 1997. 

D. Nicoll Griffith, M. Scartozzi, and N. Chiem, Automated deri-vatization and HPLC analysis of ibuprofen enantiomers, J. Chromatogr., /4655 253 (1993). 

For exanple, it can be seen in Fig. 3, that the highest possible k values for the phenolic solutes are lower than desirable, even in pure water as eluent. The solubility of these phenolic compounds is also low in pure water. Therefore, as a oenpremise between the opposing requirements of sufficient retention and high solubility, a carrier solution oenpositien of 10 % methanol water was selected for the further studies. Similarly, it can be seen from Fig. 5, that the k values of the Ibuprofen enantiomers are around 10 in the 30 % acetonitrile buffer eluent, therefore this conposition was selected for the carrier solution for the displacement chromatographic studies. 

Aromatic phenols and alcohols were also found to act as good displacers on cyclodextrin-silica columns (67,69). Since the retention studies discussed above indicate that p-nitrophenol is more retained (Fig. 2) than the chloroaniline isomers (Fig. 3), and 4-t-butyl cyclohexanol is more retained than the Ibuprofen enantiomers (Fig. 4), p-nitrophenol and 4-t-butylcyclohexanol were selected as possible displacers for the separations discussed below. 

Since the chloroanilines are sufficiently retained (k >5) in a 10 % v/v methanol water eluent, and the Ibuprofen enantiomers are sufficiently retained in a 30 % v/v acetonitrile buffer eluent, these solvents were selected as carrier solvents for the displacement chromatographic separations. Also, these solvents were used to determine the adsorption isotherms of p-nitrophenol and 4-t-butylcyclohexanol on beta-cyclodextrin silica. The isotherms were determined from frontal chromatographic measurements as described in (56). The isotherms are shown in Figs. 7 and 8. Since both isotherms are downwardly convex, p-nitrophenol and 4-t-butylcyclohexanol might prove useful displacers for our test solutes, provided that they are more strongly adsorbed that the solutes. 

Fatty acids such as octanoic and lauric acids have also been used to reduce k (94,112). An example of the effect of octanoic acid on the retention and enantioselectivity of ibuprofen enantiomers on the HSA CSP is presented in Fig. 15 (94). In this instance, without the addition of the... 

F. Jamali, N. N. Singh, E M. Easutto, R. T. Courts, and A. S. Russell, "Pharmacokinetics of ibuprofen enantiomers in man following oral administration of tablets with different absorption rates," Pharm. Res., 5 40-43 (1988), R. T. Foster, E Jamali, A. S. Russell, and S. R. AlbeUa, "Pharmacokinetics of ketoprofen enantiomers in young and elderly arthritic patients following single and multiple doses," ]. Pharm. ScL, 77 191-195 (1988). 

E Jamali, R. Mehvar, A. S. Russell, S, Sattari, W. W. Yakimets, and J, Koo, "Human pharmacokinetics of ibuprofen enantiomers following different doses and formulations Intestinal chiral inversion,"/, Pharm. Sci., 81 221-225 (1991). 

Some biotransformations introduce an asymmetric center into a drug and these often proceed stereospeci-fically. The most common examples are hydroxylation of a secondary carbon and the reduction of ketones to secondary alcohols. Ibuprofen undergoes both co and co-l oxidation of the isobutyl side chain, and formation of the resulting carboxylic acid metabolite introduces a second asymmetric center into the molecule. Both ibuprofen enantiomers have been shown to undergo stereospecific oxidation to give a metabolite with the same configuration at the new asymmetric center. 

Williams, K. Day, R. Knihinicki, R. Duffield, A. The stereoselective uptake of ibuprofen enantiomers into adipose tissue. Biochem. Pharmacol. 1986, 35 (19), 3403-3405. 

In addition, the lesser active (A)-ibuprofen enantiomer (experts called it the distomer, see Chapter 26) and a few... 

Evans, A.M. Nation, R.L. Sansom, L.N. Bochner, R Somogyi, A.A. Stereoselective plasma protein binding of ibuprofen enantiomers. Eur.J.Clin.PharmacoL, 1989, 36, 283-290... 

Nicoll-Griffith, D. Scartozzi, M. Chiem, N. Automated derivatization and higdi-performance liquid chromatographic analysis of ibuprofen enantiomers. J.ChromatognA, 1993, 653, 253-259... 

Naidong, W. Lee, J.W. Development and validation of a liquid chromatographic method for the quantitation of ibuprofen enantiomers in human plasma. J.Pharm.BiomedAnal., 1994,12, 551-556 [chiral plasma LOQ 1 p.g/mL column temp 20]... 

Freneaux E, Fromenty B, Berson A, Labbe G, Degott C, Letteron P, Larrey D, Pessayre D (1990) Stereoselective and nonstereoselective effects of ibuprofen enantiomers on mitochondrial P-oxidation of fatty acids. J Pharmacol Exp Ther 255 529-535... 

Mayer, J. M., Testa, B. Pharmacodynamics, pharmacokinetics and toxicity of ibuprofen enantiomers. Drug. Put. 1997,22,1347-1366. 

Janjikhel, R.K. Adeyeye, C.M. Dissolution of ibuprofen enantiomers from coprecipitates and suspensions containing chiral excipients. Pharm. Dev. Tech. 1999, 4, 9 17. 

Jamah, F. Singh, N.N. Pasutto, F.M. Russell, A.S. Coutts, R.T. Pharmacokinetics of ibuprofen enantiomers in humans following oral administration of tablets with different absorption rates. Pharm. Res. 1988, 5, 40-43. 

Cox, S.R. Brown, M.A. Squires, D.J. Murrill, E.A. Lednicer, D. Knuth, D.W. Comparative human study of ibuprofen enantiomer plasma concentrations produced by two commercially available ibuprofen tablets. Biopharm. Drug Dispos. 1988, 9, 539-549. 

Dong, J.Q. Ni, L. Scott, C.S. Retsch-Bogart, G.Z. Smith, P.C. Pharmacokinetics of ibuprofen enantiomers in children with cystic fibrosis. J. Clin. Pharmacol. 2000, 40, 861-868. 

Oliary, J. Tod, M. Nicolas, P. Petitjean, O. Caille, G. Pharmacokinetics of ibuprofen enantiomers after single and repeated doses in man. Biopharm. Drug Dispos. 1992, 13, 337-344. 

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