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Master's Dissertation
DOI
https://doi.org/10.11606/D.59.1998.tde-04042024-163212
Document
Author
Full name
Luis Renato Pires de Abreu
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 1998
Supervisor
Committee
Bonato, Pierina Sueli (President)
Collins, Carol Hollingworth
Lopes, João Luis Callegari
Title in Portuguese
Análise enantiosseletiva da propafenona e de seus metabólitos
Keywords in Portuguese
Propafenona - resolução
Abstract in Portuguese
Várias colunas utilizando seletores quirais baseados em derivados de amilose (CHIRALPAK AD®) ou celulose (CHIRALCEL OD-H® e CHIRALCEL ODR®), e em proteínas (CHIRAL AGP® e UL TRON ES-OVM®), foram avaliadas para a resolução dos enantiômeros da propafenona (PPF), 5-hidroxipropafenona (PPF-5OH) e N-despropílpropafenona (PPF-NOR). Além disso, foi investigada a influência da composição da fase móvel na resolução da PPF e de seus principais metabólitos. Os enantiômeros da PPF foram resolvidos em todas as colunas, exceto na coluna ULTRON ES-OVM®. Esta coluna, as colunas CHIRALPAK AD® e CHIRALCEL OD-H® foram adequadas para a resolução dos enantiômeros da PPF-5OH. Os enantiômeros da PPFNOR foram resolvidos nas colunas CHIRALPAK AD®, CHIRAL AGP® e CHIRALCEL ODR®. A coluna CHIRALPAK AD® foi a única que apresentou resolução adequada da PPF e de seus metabólitos, contudo os picos obtidos para a PPF-NOR não foram simétricos nas condições empregadas. Finalmente, foi desenvolvido um método enantiosseletivo para a determinação simultânea dos enantiômeros da PPF e PPF-5OH em plasma. Após a extração líquido-líquido com diclorometano, os enantiômeros foram resolvidos na coluna CHIRALPAK AD®, utilizando a mistura hexano-etanol (88:12) acrescida de 0,1% de dietilamina como fase móvel, com detecção em 315 nm. O procedimento de extração apresentou recuperações absolutas de 62,9% e 61,3% para a (R)- e (S)-PPF, respectivamente, e de 57,6% e 56,5% para (R)- e (S)-PPF-5OH, respectivamente. O método permitiu a determinação dos enantiômeros da PPF e PPF-5OH no intervalo de concentrações plasmáticas de 25-1250 ng/mL, podendo ser utilizados em estudos clínicos de disposição cinética.
Title in English
Enantioselective analysis of propafenone and its metabolites
Keywords in English
Propafenone - resolution
Abstract in English
Several columns, which are based on amylose (CHIRALPAK AD®) or cellulose (CHIRALCEL OD-H® and CHIRALCEL OD-R®) derivatives, and on proteins (CHIRAL AGP® and ULTRON ES-OVM®) as the chiral selectors, were evaluated for the resolution of the enantiomers of propafenone (PPF), 5-hydroxypropafenone (PPF-5OH) and N-despropylpropafenone (PPF-NOR). Furthermore, the influence of the mobile phase composition on the resolution of PPF and of its main metabolites was investigated. The enantiomers of PPF were resolved on all columns, except for the UL TRON ES-OVM® . This column, the CHIRALPAK AD® and the CHIRALCEL OD-H® columns were suitable for the resolution of the PPF-5OH enantiomers. The PPF-NOR enantiomers were resolved on the CHIRALPAK AD®, CHIRAL AGP® and CHIRALCEL OD-R® columns. The CHIRALPAK AD® column proved to be the only one useful for the resolution of PPF and of its main metabolites, although the peaks obtained for PPF-NOR were not symmetrical under the conditions investigated. Finally, an enantioselective high-performance liquid chromatography method was developed for the simultaneous determination of PPF and PPF-5OH enantiomers in plasma. After liquid-liquid extraction with dichloromethane, the enantiomers were resolved on the CHIRALPAK AD® column using hexane-ethanol (88:12) plus 0.1% diethylamine as the mobile phase and monitored at 315 nm. The extraction procedure resulted in absolute recoveríes of 62.9% and 61.3% for (R)- and (S)-PPF, respectively, and of 57.6% and 56.5% for (R)- and (S)-PPF-5OH, respectívely. The method allows the determination of PPF and PPF-SOH enantiomers at the...
 
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