ISSN:0899-0042    

DOI:10.1002/chir.530010102

出版商:Alan R. Liss, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractThe current regulatory position of the Food and Drug Administration is discussed with regard to the approval of racemates and pure stereoisomers. Circumstances in which stereochemically sensitive analytical methods are necessay to ensure the safety and efficacy of a drug are described. Regulatory guidelines are interpreted for applications for the approval of a pure enantiomer in which the racemate is marketed, for the approval of eitehr a racemate or a pure enantiomer in which neither is marketed, and for clinical investigations to compare the safety and efficacy of a racemate and its enantiomers. Examples of te basis for such regulation are drawn from historical situations (thalidomide, benoxaprofen) as well as currently marketed drugs (arylproionic acids, disopyramide, indacrinone).

ISSN:0899-0042    

DOI:10.1002/chir.530010103

出版商:Alan R. Liss, Inc.    

年代:1989

数据来源: WILEY

ISSN:0899-0042    

DOI:10.1002/chir.530010104

出版商:Alan R. Liss, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractThe pharmacokinetics of (S)‐propranolol were compared after the oral administration of a 40 mg dose of the pure enantiomer and an 80 mg dose of a racemic mixture of (R,S)‐propranolol. The results of this study indicate that the bioavailability of (S)‐propranolol, as expressed by the mean area uner the concentration‐time curve (AUC) and maximum serum concentration, is lower after 40mg of the optically pure drug than after the racem

ISSN:0899-0042    

DOI:10.1002/chir.530010105

出版商:Alan R. Liss, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractAfter alkylation of a fraction of the total α‐adrenoreceptors by phenoxybenzamine in rat vas deferens, the dissociation constants of (−)‐ and (+)‐epinephrine in functional studies were 7 × 10−7Mand 2 × 10−5M, respectively. In the adrenoreceptor‐containing tissue fraction, when3H‐labeled WB4101 was used as the interacting ligand, for each enantiomer who affinity sites were found. Only the low‐affinity dissociation consant for each isomer correlates with the constant obtained from the functional studies. If the change in Gibb's free energy. ΔG°, is calculated from the low‐affinity binding constants, the values −8.1 and −6.2 kcal/mol for (−)‐ and (+)‐isomer, respectively, are obained. The small difference in the value between isomers forms a hydrogen bond with the receptor. The interaction of epinephrine with this receptor appears to be driven largely by the entropy of the drug‐receptor interaction with only a small nonsteroselective contribu

ISSN:0899-0042    

DOI:10.1002/chir.530010106

出版商:Alan R. Liss, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractThe purpose of this work was to develop and validate a method for the separation and determination of the enantiomers of terbutaline in plasma and intestinal juice. Terbutaline was extracted from plasma and intestinal juice by liquid‐solid extraction on small C18cartridges. The extract was then analyzed by coupled column liquid chromatography with amperometric detecton. For ciral separation a β‐cyclodextrin phase was used.The within‐day variation (Cv) on spiked plasma samples was in the rane 0.8‐6.4% at 3.8‐33.8 nmol/liter for the (−)‐enantiomer, and 2.6‐23.0% at 1.3‐11.3 nmol/liter for the (+)‐enantiomer. The between‐day variation on spiked plasma samples was 5.5% at 10.7 nmol/liter and 13.6% at 4.3 nmol/liter for the (−)‐ and (+)‐enantiomers, respectively. The within‐day variation for inestinal juice was i the range 0.7‐1.5% at 5.6‐30.0

ISSN:0899-0042    

DOI:10.1002/chir.530010107

出版商:Alan R. Liss, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractA brief review of sugar stereochemistry is given. The separation of 84 different pairs of anomers was accomplished on both α‐ and β‐cyclodextrin columns. Five different mobile phases were evaluated. The separation of anomers temperature, flow rate, and so on. The separation of anomers that mutarotate is somewhat more difficult than those that do not. Prior knowledge as to the rate of mutaroation is useful so that the chromatographic conditions can be arranged to minimize any deleterious effects on the separ

ISSN:0899-0042    

DOI:10.1002/chir.530010108

出版商:Alan R. Liss, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractThe stereochemical separation of free and derivatized amino acids on active α‐chymotrypsin bonded to silica is governed by two mechanisms based on the structure of the solutes or on the enzymatic activity of the enzyme. Te deactivation of the hydrolytically active site of the enzyme demonstrated that a significant portion of the retention on this support is due to hydrophobic interactions at other sites. These sites appear to be stereoselective for the ester derivatives of amino acids but not for the other studied solut

ISSN:0899-0042    

DOI:10.1002/chir.530010109

出版商:Alan R. Liss, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractChromatographic applications of three novel chiral stationary phases (CSPs) deriving from (S)‐(N)‐(3,5‐dinitrobenzoyl)tyrosine are reported, under liquid chromatographic (LC) and subscritical fluid chromatographic (SubFC) conditions. Two grafting modes of the chiral moiety have been experimented starting either from γ‐mercaptopropyl‐silanized (type 1) or γ‐aminopropyl‐silanized (type 2) silica gels. For type 2 CSPs an evaluation of the stability of the amide linkage was achieved by means of SubFC; the relative contriution of ionic and covalent bindings to the ciral recognitio aility was then outlined. The chromatographic properties of these CSPs were compared with those of the corresponding CSPs deriving from phenylglycine,p‐hydroxyphenylglycine, and phenylalanine for the resolution of some tertiary phosphine oxide, naphthoyl amide, and α‐methylene γ‐lactam enantiomers. Some simple requirements regarding the solute and CSP structures for chiral recognition ability can be inferred from these results. In addition, the resolutio of π‐acid α‐N‐(3,5‐dinitrobenzoyl)amino esters was investigated on these π‐acid CSPs. An example of preparative sc

ISSN:0899-0042    

DOI:10.1002/chir.530010110

出版商:Alan R. Liss, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractA chiral statonary phase (CSP) derived from anN‐(3,5‐dinitrobenzoyl)‐α‐aminobenzylphosphonate has been prepared and evaluated for its utility in the direct separation of enantiomers. This CSP, 2, is structurally related to earlierN‐(3,5‐dinitrobenzoyl)‐α‐acids acid‐derived phases (e.g., CSP 1), but the mode of attachment to the support is different. In scope; CSP 2 isqualitaivelysimilar to CSP 1. However, it differsquantitativelyfrom CSP 1, showing either greater or lesser selectivity for different p

ISSN:0899-0042    

DOI:10.1002/chir.530010111

出版商:Alan R. Liss, Inc.    

年代:1989

数据来源: WILEY