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1.
Psychiatry Res ; 271: 526-531, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30553099

RESUMO

Low self-esteem is an important factor influencing mobile phone addiction, which has been well documented. However, little research focused on the mechanism underlying the association between self-esteem and mobile phone addiction. We hypothesized that social anxiety and interpersonal sensitivity may mediate the relationship between self-esteem and mobile phone addiction. Six hundred and fifty three (353 girls among them) college students with the mean age of 19.94 (SD = 1.34) were recruited for the study. Participants completed mobile phone addiction scale, Rosenberg self-esteem scale, the social anxiety questionnaire and interpersonal sensitivity subscale of SCL-90. The findings were as follows: 1) interpersonal sensitivity mediated the relation between self-esteem and mobile phone addiction. 2) social anxiety and interpersonal sensitivity sequentially mediated the relation between self-esteem and mobile phone addiction. The result reveals that self-esteem has indirect effect on mobile phone addiction, which is mediated by social anxiety and interpersonal sensitivity.


Assuntos
Ansiedade/psicologia , Comportamento Aditivo/psicologia , Telefone Celular , Autoimagem , Adolescente , Feminino , Humanos , Masculino , Estudantes , Inquéritos e Questionários , Adulto Jovem
2.
Anal Chem ; 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30451489

RESUMO

Previously, we reported a new online capillary isoelectric focusing-mass spectrometry (CIEF-MS) method for intact monoclonal antibody (mAb) charge variant analysis using an electrokinetically pumped sheath-flow nanospray ion source on a time-of-flight (TOF) MS with a pressure-assisted chemical mobilization. The direct online CIEF-MS method exhibited excellent charge variants resolution conforming to those of imaged CIEF-UV (iCIEF-UV). However, for complex mAbs, CIEF-MS spectra of the intact charge variant peaks may be overly convoluted to be effectively interpreted. In the current study, we implemented a middle-up approach to enhance the capability of the CIEF-MS method for characterizing complex mAbs charge variants by reducing sample complexity. To demonstrate such a strategy, we fragmented cetuximab through IdeS enzymatic cleavage and dithiothreitol (DTT) reduction. For the first time, online CIEF-MS resolved the complex charge variants of cetuximab at subunit level, corroborating the profiles obtained by iCIEF-UV. Furthermore, high resolution TOF mass spectra with high mass accuracy were obtained for the eight charge variants separated by CIEF-MS after IdeS cleavage, and for the eleven charge variants after IdeS digestion with subsequent DTT reduction. In-depth analyses revealed the identities of all charge variants, and pinpointed the causes of charge heterogeneity, which are in accord with those reported in the literature. The main sources of charge heterogeneity of cetuximab were identified as terminal lysine on the Fc domain (up to one on each single chain Fc), glycolyl neuraminic acid residues on the Fd' domain (up to two on each Fd'), and likely several deamidation species on the Fd' domain. No charge heterogeneity contribution was found from light chain. The in-depth characterization of complex charge variants for cetuximab demonstrates the remarkable capability of this middle-up CIEF-MS approach. This novel workflow holds great potential for detecting and elucidating charge variants to help understand protein with complex charge heterogeneity.

3.
Anal Chem ; 90(3): 2246-2254, 2018 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-29272582

RESUMO

We report a new online capillary isoelectric focusing-mass spectrometry (CIEF-MS) method for monoclonal antibody (mAb) charge variant analysis using an electrokinetically pumped sheath-flow nanospray ion source and a time-of-flight MS with pressure-assisted chemical mobilization. To develop a successful, reliable CIEF-MS method for mAb, we have selected and optimized many critical, interrelating reagents and parameters that include (1) MS-friendly anolyte and catholyte; (2) a glycerol enhanced sample mixture that reduced non-CIEF electrophoretic mobility and band broadening; (3) ampholyte selected for balancing resolution and MS sensitivity; (4) sheath liquid composition optimized for efficient focusing, mobilization, and electrospray ionization; (5) judiciously selected CIEF running parameters including injection amount, field strength, and applied pressure. The fundamental premise of CIEF was well maintained as verified by the linear correlation (R2 = 0.99) between pI values and migration time using a mixture of pI markers. In addition, the charge variant profiles of trastuzumab, bevacizumab, infliximab, and cetuximab, obtained using this CIEF-MS method, were corroborated by imaged CIEF-UV (iCIEF-UV) analyses. The relative standard deviations (RSD) of absolute migration time of pI markers were all less than 5% (n = 4). Triplicate analyses of bevacizumab showed RSD less than 1% for relative migration time to an internal standard and RSD of 7% for absolute MS peak area. Moreover, the antibody charge variants were characterized using the online intact MS data. To the best of our knowledge, this is the first time that direct online MS detection and characterization were achieved for mAb charge variants resolved by CIEF as indicated by a well-established linear pH gradient and correlated CIEF-UV charge variant profiles.

4.
J Chromatogr A ; 1530: 176-184, 2017 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-29162234

RESUMO

During a preparative separation of the cis enantiomeric pair of benzyl-2,3-dihydroxypiperidine-1-carboxylate using supercritical-fluid chromatography (SFC) with methanol modifier, significant degradation of the products in the collected fractions was observed when a Waters SFC-350® (Milford, MA, USA) was used, but same was not observed when a Waters SFC-80q® (Milford, MA, USA) was used. Through a systematic investigation, we discovered that the compound degraded over time under an acidic condition created by the formation of methyl carbonic acid from methanol and CO2. The extent of the product degradation was dependent on the time and the concentration of CO2 remained in the product fraction, which was governed by the efficiency of CO2-methanol separation during the fraction collection. Hence, we demonstrated that the different designs of CO2-solvent separator (high pressurized cyclone in Waters SFC-350® and low-pressurized vortexing separator in Waters SFC-80q®®) had a significant impact on the degradation of an acid-sensitive compound. The acidity caused by CO2 in methanol was supported by diminished degradation after a nitrogen purging or after neutralizing the collected fractions with a base. Three different solutions to overcome the degradation problem of the acid sensitive compounds using SFC-350® with the high pressurized separator were investigated and demonstrated. The degraded products were isolated as four enantiomers and their relative stereochemistry were established based on 2D NMR data along with the plausible mechanism of degradation.


Assuntos
Dióxido de Carbono/química , Ácidos Carboxílicos/química , Cromatografia com Fluido Supercrítico , Solventes/química , Ácido Carbônico/química , Metanol/química , Piperidinas/química , Pressão , Estereoisomerismo
5.
J Chromatogr A ; 1487: 116-128, 2017 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-28131592

RESUMO

Atropisomers are stereoisomers resulting from hindered bond rotation. From synthesis of pure atropisomers, characterization of their interconversion thermodynamics to investigation of biological stereoselectivity, the evaluation of drug candidates subject to atropisomerism creates special challenges and can be complicated in both early drug discovery and later drug development. In this paper, we demonstrate an array of analytical techniques and systematic approaches to study the atropisomerism of drug molecules to meet these challenges. Using a case study of Bruton's tyrosine kinase (BTK) inhibitor drug candidates at Bristol-Myers Squibb, we present the analytical strategies and methodologies used during drug discovery including the detection of atropisomers, the determination of their relative composition, the identification of relative chirality, the isolation of individual atropisomers, the evaluation of interconversion kinetics, and the characterization of chiral stability in the solid state and in solution. In vivo and in vitro stereo-stability and stereo-selectivity were investigated as well as the pharmacological significance of any changes in atropisomer ratios. Techniques applied in these studies include analytical and preparative enantioselective supercritical fluid chromatography (SFC), enantioselective high performance liquid chromatography (HPLC), circular dichroism (CD), and mass spectrometry (MS). Our experience illustrates how atropisomerism can be a very complicated issue in drug discovery and why a thorough understanding of this phenomenon is necessary to provide guidance for pharmaceutical development. Analytical techniques and methodologies facilitate key decisions during the discovery of atropisomeric drug candidates by characterizing time-dependent physicochemical properties that can have significant biological implications and relevance to pharmaceutical development plans.


Assuntos
Cromatografia Líquida de Alta Pressão , Cromatografia com Fluido Supercrítico , Descoberta de Drogas/métodos , Proteínas Tirosina Quinases/antagonistas & inibidores , Tirosina Quinase da Agamaglobulinemia , Dicroísmo Circular , Descoberta de Drogas/instrumentação , Cinética , Espectrometria de Massas , Estereoisomerismo , Termodinâmica
7.
J Med Chem ; 59(19): 9173-9200, 2016 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-27583770

RESUMO

Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase, is a member of the Tec family of kinases. BTK plays an essential role in B cell receptor (BCR)-mediated signaling as well as Fcγ receptor signaling in monocytes and Fcε receptor signaling in mast cells and basophils, all of which have been implicated in the pathophysiology of autoimmune disease. As a result, inhibition of BTK is anticipated to provide an effective strategy for the clinical treatment of autoimmune diseases such as lupus and rheumatoid arthritis. This article details the structure-activity relationships (SAR) leading to a novel series of highly potent and selective carbazole and tetrahydrocarbazole based, reversible inhibitors of BTK. Of particular interest is that two atropisomeric centers were rotationally locked to provide a single, stable atropisomer, resulting in enhanced potency and selectivity as well as a reduction in safety liabilities. With significantly enhanced potency and selectivity, excellent in vivo properties and efficacy, and a very desirable tolerability and safety profile, 14f (BMS-986142) was advanced into clinical studies.


Assuntos
Carbazóis/química , Carbazóis/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Tirosina Quinase da Agamaglobulinemia , Animais , Carbazóis/farmacocinética , Cristalografia por Raios X , Feminino , Humanos , Isomerismo , Macaca fascicularis , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Inibidores de Proteínas Quinases/farmacocinética , Proteínas Tirosina Quinases/metabolismo , Quinazolinas/química , Quinazolinas/farmacocinética , Quinazolinas/farmacologia , Relação Estrutura-Atividade
8.
J Med Chem ; 59(17): 7915-35, 2016 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-27531604

RESUMO

Bruton's tyrosine kinase (BTK) belongs to the TEC family of nonreceptor tyrosine kinases and plays a critical role in multiple cell types responsible for numerous autoimmune diseases. This article will detail the structure-activity relationships (SARs) leading to a novel second generation series of potent and selective reversible carbazole inhibitors of BTK. With an excellent pharmacokinetic profile as well as demonstrated in vivo activity and an acceptable safety profile, 7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide 6 (BMS-935177) was selected to advance into clinical development.


Assuntos
Antirreumáticos/química , Carbazóis/química , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinazolinonas/química , Administração Oral , Tirosina Quinase da Agamaglobulinemia , Animais , Antirreumáticos/síntese química , Antirreumáticos/farmacocinética , Antirreumáticos/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Disponibilidade Biológica , Carbazóis/síntese química , Carbazóis/farmacocinética , Carbazóis/farmacologia , Linhagem Celular , Cristalografia por Raios X , Cães , Humanos , Macaca fascicularis , Camundongos , Microssomos Hepáticos/metabolismo , Permeabilidade , Proteínas Tirosina Quinases/química , Quinazolinonas/síntese química , Quinazolinonas/farmacocinética , Quinazolinonas/farmacologia , Relação Estrutura-Atividade
9.
J Chromatogr A ; 1455: 133-139, 2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-27286648

RESUMO

UV spectrophotometry is widely used to determine the molar extinction coefficients (MECs) of cytotoxic drugs as well as the drug antibody ratios (DARs) of antibody drug conjugates (ADCs). However, the unknown purity of a drug due to interfering impurities can lead to erroneous MECs and DARs. Hence, reliable methods to accurately determine purity and the MECs of drugs with limited quantity is urgently needed in Drug Discovery. Such a method has been developed. It achieves absolute purity and accurate MEC determination by a single automated HPLC analysis that uses less than 5µg of material. Specifically, analytical HPLC separation with online UV detection was used to resolve impurities and measure absorbance from only the compound of interest. Simultaneously, an online chemiluminescence nitrogen detector (CLND) was used to determine the concentration of the analyte. The MECs were then calculated from the absorbance and concentration results. The accuracy of the method was demonstrated using caffeine and a commercial cytotoxic drug, DM1. This approach is particularly suited to analyzing mixtures or samples with low purities. Excellent reproducibility was demonstrated by analyzing a proprietary drug with linker synthesized from different batches with very different levels of purity. In addition, the MECs of drug with linker, along with ADC peak areas measured from size exclusion chromatography (SEC), were used to calculate DARs for 21 in-house ADCs. The DAR results were consistent with those obtained by MS analysis.


Assuntos
Anticorpos/química , Antineoplásicos Fitogênicos/química , Imunoconjugados/química , Maitansina/análogos & derivados , Anticorpos/imunologia , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Medições Luminescentes , Espectrometria de Massas , Maitansina/química , Nitrogênio/análise , Espectroscopia de Prótons por Ressonância Magnética , Espectrofotometria Ultravioleta
10.
Int J Pharm ; 514(2): 364-373, 2016 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-27291974

RESUMO

A comprehensive 8-drug metabolic cocktail was designed to simultaneously target 6 Cytochrome P450 enzymes and 2 membrane transporters. This study aimed to assess the pre-absorption risk of this new metabolic cocktail which contained metoprolol, caffeine, midazolam, pravastatin, flurbiprofen, omeprazole, digoxin and montelukast. This paper describes a systematic approach to understand whether the co-administration of the 8 selected drug products, i.e., the physical mixing of these products in the human gastro-intestinal environment, will create any issue that may interfere with the individual drug dissolution which in turns modify the total amount or timing of their availability for absorption. The evaluation consisted of two steps. An initial evaluation was based on theoretical understanding of the physicochemical properties of the drugs and the gastro intestinal environment, followed by in vitro dissolution tests. The results indicated that the designer 8-drug cocktail has acceptable pre-absorption compatibility when dosed simultaneously, and recommended the progression of the cocktail into clinical validation study.


Assuntos
Combinação de Medicamentos , Interações de Medicamentos , Fenômenos Químicos , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio
11.
J Pharmacol Exp Ther ; 357(2): 382-93, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26907622

RESUMO

Inhibition of organic anion-transporting polypeptide (OATP)1B function can lead to serious clinical drug-drug interactions, thus a thorough evaluation of the potential for this type of interaction must be completed during drug development. Therefore, sensitive and specific biomarkers for OATP function that could be used in conjunction with clinical studies are currently in demand. In the present study, preclinical evaluations were conducted to characterize the suitability of coproporphyrins (CPs) I and III as markers of hepatic OATP functional activity. Active uptake of CPs I and III was observed in human embryonic kidney (HEK) 293 cells singly expressing human OATP1B1 (hOATP1B1), hOATP1B3, cynomolgus monkey OATP1B1 (cOATP1B1), or cOATP1B3, as well as human and monkey hepatocytes. Cyclosporin A (100 mg/kg, oral) markedly increased the area under the curve (AUC) plasma concentrations of CPs I and III by 2.6- and 5.2-fold, while rifampicin (15 mg/kg, oral) increased the AUCs by 2.7- and 3.6-fold, respectively. As the systemic exposure increased, the excretion of both isomers in urine rose from 1.6- to 4.3-fold in monkeys. In agreement with this finding, the AUC of rosuvastatin (RSV) in cynomolgus monkeys increased when OATP1B inhibitors were coadministered. In Oatp1a/1b gene cluster knockout mice (Oatp1a/1b(-/-)), CPs in plasma and urine were significantly increased compared with wild-type animals (7.1- to 18.4-fold; P < 0.001), which were also in agreement with the changes in plasma RSV exposure (14.6-fold increase). We conclude that CPs I and III in plasma and urine are novel endogenous biomarkers reflecting hepatic OATP function, and the measurements have the potential to be incorporated into the design of early clinical evaluation.


Assuntos
Coproporfirinas/sangue , Transportadores de Ânions Orgânicos/genética , Animais , Área Sob a Curva , Ciclosporina/farmacocinética , Células HEK293 , Hepatócitos/metabolismo , Humanos , Transportador 1 de Ânion Orgânico Específico do Fígado , Macaca fascicularis , Camundongos , Camundongos Knockout , Transportadores de Ânions Orgânicos/administração & dosagem , Transportadores de Ânions Orgânicos/metabolismo , Rifampina/farmacocinética , Rosuvastatina Cálcica/farmacocinética
12.
J Chromatogr A ; 1426: 133-9, 2015 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-26674608

RESUMO

Two dimensional liquid chromatography (2D-LC) coupling size exclusion (SEC) and hydrophilic interaction chromatography (HILIC) is demonstrated as a useful tool to study polar excipients, such as histidine and its degradant, in protein formulation samples. The SEC-HILIC setup successfully removed interferences from complex sample matrices and enabled accurate mass measurement of the histidine degradation product, which was then determined to be trans-urocanic acid. Because the SEC effluent is a strong solvent for the second dimension HILIC, experimental parameters needed to be carefully chosen, i.e., small transferring loop, fast gradient at high flow rates for the second dimension gradient, in order to mitigate the solvent mismatch and to ensure good peak shapes for HILIC separations. In addition, the generation of trans-urocanic acid was quantified by single heart-cutting SEC-HILIC 2D-LC combined with stable-isotope labeling mass spectrometry. Compared with existing 2D quantification methods, the proposed approach is fast, insensitive to solvent mismatch between dimensions, and tolerant of small retention time shifts in the first dimension. Finally, the first dimension diode array detector was found to be a potential degradation source for photolabile analytes such as trans-urocanic acid.


Assuntos
Cromatografia Líquida/métodos , Fibronectinas/química , Histidina/química , Isótopos de Carbono , Química Farmacêutica , Cromatografia em Gel , Interações Hidrofóbicas e Hidrofílicas , Marcação por Isótopo , Espectrometria de Massas/métodos , Isótopos de Nitrogênio
14.
J Org Chem ; 80(14): 7019-32, 2015 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-26151079

RESUMO

Clopidogrel is a prodrug anticoagulant with active metabolites that irreversibly inhibit the platelet surface GPCR P2Y12 and thus inhibit platelet activation. However, gaining an understanding of patient response has been limited due to imprecise understanding of metabolite activity and stereochemistry, and a lack of acceptable analytes for quantifying in vivo metabolite formation. Methods for the production of all bioactive metabolites of clopidogrel, their stereochemical assignment, and the development of stable analytes via three conceptually orthogonal routes are disclosed.


Assuntos
Microssomos Hepáticos/metabolismo , Piperidinas/síntese química , Inibidores da Agregação de Plaquetas/síntese química , Inibidores da Agregação de Plaquetas/metabolismo , Pró-Fármacos/síntese química , Ticlopidina/análogos & derivados , Fenômenos Biológicos , Clopidogrel , Humanos , Microssomos Hepáticos/efeitos dos fármacos , Piperidinas/química , Inibidores da Agregação de Plaquetas/química , Pró-Fármacos/química , Estereoisomerismo , Ticlopidina/síntese química , Ticlopidina/química , Ticlopidina/metabolismo
15.
ACS Med Chem Lett ; 6(7): 770-5, 2015 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-26191364

RESUMO

A series of dimeric macrocyclic compounds were prepared and evaluated as antagonists for inhibitor of apoptosis proteins. The most potent analogue 11, which binds to XIAP and c-IAP proteins with high affinity and induces caspase-3 activation and ultimately cell apoptosis, inhibits growth of human melanoma and colorectal cell lines at low nanomolar concentrations. Furthermore, compound 11 demonstrated significant antitumor activity in the A875 human melanoma xenograft model at doses as low as 2 mg/kg on a q3d schedule.

16.
ACS Med Chem Lett ; 6(5): 523-7, 2015 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-26005526

RESUMO

Structure-activity relationships in a series of (2-oxo-1,4-benzodiazepin-3-yl)-succinamides identified highly potent inhibitors of γ-secretase mediated signaling of Notch1/2/3/4 receptors. On the basis of its robust in vivo efficacy at tolerated doses in Notch driven leukemia and solid tumor xenograft models, 12 (BMS-906024) was selected as a candidate for clinical evaluation.

17.
Bioorg Med Chem Lett ; 25(9): 1905-9, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25857941
18.
Pharm Res ; 32(8): 2625-35, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25670525

RESUMO

PURPOSE: An unknown UV 280 nm absorbing peak was observed by SEC for protein stability samples formulated in L-histidine during a stress stability study. Understanding the source would enhance the confidence in the SEC results. We identified the unknown peak, studied the cause, and evaluated ways to eliminate it. METHODS: The unknown peak was fractionated by preparative size exclusion chromatography separations, and subsequently analyzed by Hydrophilic Interaction Chromatography (HILIC) coupled with Time-of-Flight (TOF) high resolution mass spectrometry. The possible degradation was also studied with the presence of different excipients, including metal cations, chelating agents, and amino acids. RESULTS: The unknown peak was identified to be trans-urocanic acid, a degradant of histidine, based on evidences from HILIC retention time, UV profile, accurate mass measurement, trans-cis isomerization, and pI measurement. The degradation from histidine to urocanic acids was not affected by the presence of Fe(2+), but slightly activated by Mn(2+). The chelating agents, EDTA and DTPA, counteracted the Mn(2+) effects. This degradation was evidenced to be caused by contamination. Adding alanine or cysteine as an excipient was found to reduce this degradation by 97 and 98%, respectively. CONCLUSIONS: L-histidine formulation buffer can be contaminated to induce histidine degradation to trans-urocanic acid, which shows a large UV 280 nm absorbing peak at the total permeation volume under SEC conditions. Amino acids alanine and cysteine effectively inhibit this histidine degradation.


Assuntos
Produtos Biológicos/administração & dosagem , Produtos Biológicos/química , Histidina/química , Ácido Urocânico/química , Tampões (Química) , Quelantes/química , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Contaminação de Medicamentos , Estabilidade de Medicamentos , Excipientes/química , Espectrometria de Massas , Proteínas/química , Espectrofotometria Ultravioleta
19.
J Chromatogr A ; 1363: 278-93, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-25035237

RESUMO

The majority of published enantiomeric separations by supercritical fluid chromatography (SFC) utilize chiral stationary phases (CSP) based on chemically derivatized amylose or cellulose, coated or immobilized on silica. There is a large diversity among these polysaccharide-type CSP enhancing the scope of chiral separation applications. But on the other hand, identifying the appropriate support for a given separation problem is rather difficult. Hence, this study aims to provide insights on the difference and similarity among the non-halogenated polysaccharide CSP in terms of retention and selectivity at a molecular level. Firstly, the potential of the clones provided by different manufacturers is evaluated with carbon dioxide - methanol mobile phases. Then different aspects of the chiral recognition mechanism contributing to the separations on 16 different columns of five distinct chiral selectors will be explored based on a large amount of experimental data acquired with the help of modelling and chemometric techniques. We report the influence of the ligand bonded to the polysaccharide on the non-enantio-specific interactions between the solute and the CSP, comparing phenylcarbamate to 3,5-dimethylphenylcarbamate, and 4-methylphenylester to 3,5-dimethylphenylcarbamate. In addition, we evaluate the impact of the silica treatment on the quality of the separation. The phases are characterized in terms of their retention characteristics assessed by the solvation parameter model and separation capabilities assessed by discriminant analysis.


Assuntos
Cromatografia com Fluido Supercrítico/métodos , Polissacarídeos/química , Estereoisomerismo
20.
J Chromatogr A ; 1363: 294-310, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-24973802

RESUMO

The chiral recognition mechanism for a successful enantioseparation on polysaccharide stationary phases are still poorly understood. In this series of papers, we aim to provide some insight into the retention and separation mechanisms occurring in enantioselective supercritical fluid chromatography (SFC). This paper presents a thorough investigation on chlorinated polysaccharide chiral stationary phases (CSP) comprising five coated and three immobilized phases from different manufacturers. The columns are also compared to four non-chlorinated phases to unravel the most significant differences brought about by the introduction of electron-withdrawing atoms on the aromatic ligands. Chemometrics are used to (i) get an overview of all columns (cluster analysis), (ii) describe retention (modified solvation parameter model) and (iii) describe enantioseparation (discriminant analysis). Sample applications are provided to support the discussion.


Assuntos
Cromatografia com Fluido Supercrítico/métodos , Polissacarídeos/química , Análise por Conglomerados , Análise Discriminante , Estereoisomerismo
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