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Titolo:
Simultaneous determination of enantioselective plasma protein binding of aminohydantoins by ultrafiltration and chiral high-performance liquid chromatography
Autore:
Peng, SX; Henson, C; Wilson, LJ;
Indirizzi:
Procter & Gamble Co, Hlth Care Res Ctr, Mason, OH 45040 USA Procter & Gamble Co Mason OH USA 45040 Care Res Ctr, Mason, OH 45040 USA
Titolo Testata:
JOURNAL OF CHROMATOGRAPHY B
fascicolo: 1, volume: 732, anno: 1999,
pagine: 31 - 37
SICI:
1387-2273(19990910)732:1<31:SDOEPP>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
BETA-CYCLODEXTRIN; SEPARATION; COLUMN; DRUGS;
Keywords:
binding constants; plasma protein binding; hydantoin; proteins; aminohydantoins;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
10
Recensione:
Indirizzi per estratti:
Indirizzo: Peng, SX Procter & Gamble Co, Hlth Care Res Ctr, 8700 Mason Montgomery Rd,Mason, OH 45040 USA Procter & Gamble Co 8700 Mason Montgomery Rd Mason OH USA 45040 A
Citazione:
S.X. Peng et al., "Simultaneous determination of enantioselective plasma protein binding of aminohydantoins by ultrafiltration and chiral high-performance liquid chromatography", J CHROMAT B, 732(1), 1999, pp. 31-37

Abstract

Chiral HPLC methods were developed and utilized for the simultaneous determination of plasma protein binding of enantiomers of two racemic aminohydantoin compounds. Reversed-phase HPLC with the use of a polysaccharide-type chiral stationary phase column was employed for the separation and quantitation of the enantiomers of the two compounds with detection limits in the range 5-10 ng/ml in the plasma matrix. The chiral HPLC methods were selective, sensitive and reproducible, The R and S enantiomers of both compounds were baseline-resolved under the chromatographic conditions employed. Ultrafiltration techniques were applied to determining the plasma protein binding for each enantiomer in rat, dog and human plasma. The results clearly show stereoselective binding of the two enantiomers of each compound with higher protein binding of the R enantiomer than the S enantiomer in rat, dog and human plasma. Binding association constants were also determined to be in the range 1.01-14.0 . 10(4) M-1 at 37 degrees C. Both the protein binding percentage and binding association constant were enantioselective and species-dependent. Such information is important for a clear understanding of the differences in biological activity as well as in pharmacokinetic and pharmacodynamic properties between the two enantiomers of each compound in the drug discovery and development process. (C) 1999 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/05/20 alle ore 10:04:59