High performance capillary electrophoresis for determination of the enantiomers of 2-arylpropionic acid derivatives in human serum. Pharmacokinetic studies of ketoprofen enantiomers following administration of standard and sustained release tablets.

作者: Franciszek K. Główka , Marta Karaźniewicz

DOI: 10.1016/J.JPBA.2004.01.030

关键词:

摘要: A stereospecific capillary zone electrophoresis (CZE) method for determination of the enantiomers some 2-arylpropionic acid derivatives (2-APA, profens) in human serum has been developed. Racemic-ibuprofen (rac-IBP), racemic-flurbiprofen (rac-FBP), racemic-ketoprofen (rac-KTP) and (+)-S-naproxen ((+)-S-NPX--an internal standard) were chosen these studies. The 2-APA extracted from acidified samples using methylene chloride separated a fused silica capillary. was filled with background electrolyte, which consisted 0.05 M heptakis 2,3,6-tri-O-methyl-beta-cyclodextrin (TMbetaCD) (chiral selector) 0.02 triethanolamine-phosphate buffer pH 5.0. Separation resolution enantiomer mixture obtained one analytical run. calculated electrophoretic parameters analytes as follows: mobility, micorep(-)-R = -0.75 x 10(-4) to -0.30 cm2/Vs; micorep(+)-S -0.83 -(-0.38) cm2/Vs electroosmotic microEOF 2.35 cm2/Vs, migration times, tmigr R 12.55 - 16.07 min; s 13.08 16.9 min, factors, RS 1.88 3.70 chiral selectivity, alpha 1.16 1.34. developed validated. calibration curves linear range 0.5-50.0 microg/ml FBP or KTP 1.0-50.0 IBP concentrations. Recovery about 90%. At limit quantification (LOQ) precision accuracy within 15%. validated successfully applied pharmacokinetic bioavailability studies on humans after administration standard sustained release tablets rac-KTP. Significant differences both formulations observed studied not bioequivalent.

参考文章(14)
Anita C. Rudy, Yingxian Liu, D. Craig Brater, Stephen D. Hall, Stereoselective pharmacokinetics and inversion of (R)- ketoprofen in healthy volunteers. The Journal of Clinical Pharmacology. ,vol. 38, ,(1998) , 10.1002/J.1552-4604.1998.TB04411.X
Fabrice Lagrange, Fabienne Péhourcq, Myriam Matoga, Bernard Bannwarth, Binding of ketoprofen enantiomers in various human albumin preparations. Journal of Pharmaceutical and Biomedical Analysis. ,vol. 23, pp. 793- 802 ,(2000) , 10.1016/S0731-7085(00)00380-0
M Blanco, J Coello, H Iturriaga, S Maspoch, C Pérez-Maseda, Separation of profen enantiomers by capillary electrophoresis using cyclodextrins as chiral selectors. Journal of Chromatography A. ,vol. 793, pp. 165- 175 ,(1998) , 10.1016/S0021-9673(97)00893-5
Vinod P. Shah, Kamal K. Midha, Shrikant Dighe, Iain J. McGilveray, Jerome P. Skelly, Avraham Yacobi, Thomas Layloff, C.T. Viswanathan, C. Edgar Cook, R.D. Mcdowall, Kenneth A. Pittman, Sidney Spector, Analytical Methods Validation: Bioavailability, Bioequivalence, and Pharmacokinetic Studies Journal of Pharmaceutical Sciences. ,vol. 81, pp. 309- 312 ,(1992) , 10.1002/JPS.2600810324
Seung Joon Baek, Leigh C. Wilson, Chang-Ho Lee, Thomas E. Eling, Dual function of nonsteroidal anti-inflammatory drugs (NSAIDs): inhibition of cyclooxygenase and induction of NSAID-activated gene. Journal of Pharmacology and Experimental Therapeutics. ,vol. 301, pp. 1126- 1131 ,(2002) , 10.1124/JPET.301.3.1126
Andrew J. Hutt, John Caldwell, The metabolic chiral inversion of 2-arylpropionic acids—a novel route with pharmacological consequences Journal of Pharmacy and Pharmacology. ,vol. 35, pp. 693- 704 ,(2011) , 10.1111/J.2042-7158.1983.TB02874.X
Jiunn H. Lin, David M. Cocchetto, Daniel E. Duggan, Protein binding as a primary determinant of the clinical pharmacokinetic properties of non-steroidal anti-inflammatory drugs. Clinical Pharmacokinectics. ,vol. 12, pp. 402- 432 ,(1987) , 10.2165/00003088-198712060-00002