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  • HPLC chiral stationary phase  (2)
  • enantioselective HPLC  (2)
  • protein binding  (2)
  • (R)-albuterol  (1)
  • 1
    Electronic Resource
    Electronic Resource
    A Population Analysis of Nebulized (R)-albuterol in Dogs Using a Novel Mixed Gut-Lung Absorption PK-PD Model (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1228-1235 
    Details
    ISSN: 1573-904X
    Keywords: (R)-albuterol ; enantiomer ; population pharmacokinetic analysis ; pharmacodynamics ; nebulization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The objectives of this study were to 1) construct a pharmacokinetic-pharmacodynamic (PK-PD) model, and 2) determine the PKs and PDs of (R)-albuterol when given by nebulization to 8 dogs for 7 consecutive days. Methods. Four doses were evaluated (0.002, 0.02, 0.1, and 0.4 mg/kg/day). Blood samples were obtained after drug administration on days 1 and 7. Heart rates (HR) were obtained during treatment days 1, 4 and 7. All (R)-albuterol plasma concentrations were fitted using a mixed gut-lung absorption 2-compartment PK model. Day-1, 4, and 7 HR data were co-modeled using a direct response model with Hill-type equations, including a necessary tolerance phenomenon. The population PK-PD analysis was performed with an iterative 2-stage methodology (IT2S). Results. No chiral inversion was seen, and double absorption peaks on the plasma concentration versus time curves were observed in the majority of dogs. These were hypothesized to be the result of combined gut and lung absorption of (R)-Albuterol. Results indicated that 67% (range: 57-89%) of (R)-albuterol systemic exposure after nebulized administration is due to gut absorption. Mean population PK parameters were KaGI (10±5.7 h−1), KaLUNG (21±9.5 h−1), CLc/F (0.6±0.2 L/h/kg), CLd/F (1.4±0.5 L/h/kg), Vc/F (1.4±0.9 L/kg), and Vp/F (4.8±2.4 L/kg). (R)-albuterol administration was associated with an increase in the dogs heart rates. A tolerance effect related to the cumulative dose was observed and modeled. Conclusions. The presented PK-PD model appears to differentiate gut from lung absorption when (R)-albuterol is given by 15-minute nebulization to dogs. These results agree with the accepted hypothesis that most of the systemic exposure of (R)-albuterol after nebulized administration is due to gut absorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026466730347
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    The Measurement of Warfarin Enantiomers in Serum Using Coupled Achiral/Chiral, High-Performance Liquid Chromatography (HPLC) (1988)
    Springer
    Pharmaceutical research 5 (1988), S. 680-683 
    Details
    ISSN: 1573-904X
    Keywords: warfarin enantiomers ; achiral/chiral high-performance liquid chromatography (HPLC) ; enantioselective HPLC ; serum levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract An assay for the serum concentration of the enantiomers of warfarin, R-warfarin and S-warfarin, has been developed using a bovine serum albumin chiral stationary phase (BSA-CSP) coupled to a Pinkerton internal-surface reverse-phase (ISRP) achiral column. The ISRP column is used to separate R,S-warfarin from the serum components and warfarin metabolites and to quantitate the total R,S-warfarin concentration. The eluent containing R,S-warfarin is then selectively transferred to the BSA-CSP, where the enantiomers are stereochemically resolved (α = 1.19) and the enantiomeric composition is determined. This system is sensitive and accurate, does not require extensive precolumn manipulations, and can be automated for use in large-scale clinical studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015991324316
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    The in Situ Acetylation of an Immobilized Human Serum Albumin Chiral Stationary Phase for High-Performance Liquid Chromatography in the Examination of Drug–Protein Binding Phenomena (1992)
    Springer
    Pharmaceutical research 9 (1992), S. 480-484 
    Details
    ISSN: 1573-904X
    Keywords: chiral stationary phases ; human serum albumin ; protein binding ; binding sites ; high-performance liquid chromatography ; immobilized proteins ; chemical modification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The in situ modification of an immobilized human serum albumin (HSA) high-performance liquid chromatographic chiral stationary phase by p-nitrophenyl acetate is reported. This procedure, which is thought to affect primarily a single reactive tyrosine residue within the protein structure, influenced the chromatographic retention and enantioselectivity factors of a wide range of solutes. For certain solutes, increases in both capacity factor and chiral resolution were observed. Ultrafiltration studies on representative test solutes using free HSA, treated in a similar manner to the immobilized protein, gave similar results as the chromatographic observations, indicating that the latter effects are not artifactual results of immobilization. The effect of the modification of HSA on the binding behavior of drugs reportedly sharing the site predominantly affected by the derivatization, namely, the indole–benzodiazepine binding site, varied greatly. This observation suggests that the affected binding area is not a single, tightly structurally defined site.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015884112039
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  • 4
    Electronic Resource
    Electronic Resource
    Measurement of Underivatized Propranolol Enantiomers in Serum Using a Cellulose –Tris(3,5 -Dimethylphenylcarbamate) High-Performance Liquid Chromatographic (HPLC) Chiral Stationary Phase (1988)
    Springer
    Pharmaceutical research 5 (1988), S. 187-189 
    Details
    ISSN: 1573-904X
    Keywords: propanolol enantiomers ; enantioselective high-performance liquid chromatography (HPLC) ; HPLC chiral stationary phase ; serum levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A commercially available high-performance liquid chromatographic (HPLC) chiral stationary phase (HPLC-CSP) has been used to measure serum levels of d- and l-propranolol. The HPLC-CSP is based upon cellulose–tris(3,5-dimethylcarbamate) and is able to stereochemically resolve d- and l-propranolol without precolumn derivatization using a mobile phase composed of hexane:2-propranol:N,N-dimethyloctylamine (92:8:0.01, v/v/v). Under these conditions the observed stereochemical resolution (α) of the two enantiomers was α = 2.2. A subject's concentration–time curve of the two isomers was determined following the ingestion of 160 mg racemic propranolol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015921124857
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Immobilized serum albumin: Rapid HPLC probe of stereoselective protein-binding interactions (1990)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 2 (1990), S. 263-268 
    Details
    ISSN: 0899-0042
    Keywords: protein binding ; stereoselectivity ; immobilized human serum albumin ; HPLC chiral stationary phase ; chiral drugs ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A human serum albumin-based HPLC chiral stationary phase (HSA-CSP) has been examined as a tool to investigate binding of chiral drugs to HSA and drug-drug protein-binding interactions. Rac-oxazepam hemisuccinate (OXH) was used as a model compound and the chromatographic retention (k′) of its enantiomers was determined after addition of displacers to the mobile phase. Compounds known to bind at the same site as OXH and at different sites were tested for their displacing capacities. Competitive binding interactions between the OXH enantiomers and displacers in the mobile phase were reflected by decreases in the k′s of (R)- and (S)-OXH. The results indicate that retention on the HSA-CSP accurately reflects binding to native HSA and the technique can determine enantioselective and competitive binding interactions at specific sites on HSA. The HSA-CSP was also able to recognize separate binding areas for (S)- and (R)-OXH.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/chir.530020412
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  • 6
    Electronic Resource
    Electronic Resource
    Enantioselective separation of cyclic chiral ketones and their corresponding diastereomeric alcohols by HPLC on chiral and chiral/chiral coupled stationary phases (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 551-555 
    Details
    ISSN: 0899-0042
    Keywords: amylose tris-3,5-dimethylphenyl carbamate CSP {AD-CSP} ; cellulose tris-3,5-dimethylphenyl carbamate CSP {ODH-CSP} ; enantioselective HPLC ; coupled column chromatography ; Chemistry ; Food Science, Agricultural, Medicinal and Pharmaceutical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Enantioselective HPLC methods have been developed for the resolution of (RS)-2-phenylcyclohexanone (compound 1) and (RS)-2-phenyltetrahydropyran-4-one (compound 4) and the diastereoselective and enantioselective separations of their respective cis- and trans-alcohols; reduction of compound 1 yields trans- and cis-2-phenyl-1-cyclohexanol (compounds 2 and 3, respectively) and reduction of compound 4 yields trans- and cis-2-phenyl-tetrahydropyran-4-ol (compounds 5 and 6, respectively). Compounds 1, 2, and 3 were stereochemically resolved using a chiral stationary phase (CSP) based upon amylose tris(3,5-dimethylphenyl carbamate) coated on 10 μm silica-gel (Chiralpak AD-CSP). Compounds 4, 5, and 6 were stereochemically resolved on a coupled column system where a column containing a CSP based upon cellulose tris(3,5-dimethylphenyl carbamate) coated on 5 μm silica (Chiralcel OD-H-CSP) was coupled in series to the AD-CSP. The strategy employed in the identification of the peaks in the respective chromatograms is also discussed in this presentation. Chirality 8:551-555, 1996. © 1997 Wiley-Liss, Inc.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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