Capillary Electromigration Techniques for the Analysis of Drugs and Metabolites in Biological Matrices: A Critical Appraisal

Gaitani, Cristiane Masetto de; Oliveira, Anderson Rodrigo Moraes de; Bonato, Pierina Sueli

doi:10.1002/9781118530009.ch12

Cited by 3 publications

(1 citation statement)

References 94 publications

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“…Nesse pH, os analitos em sua forma catiônica [74], podem interagir com as CDs aniônica (CD-α-sulfatada) e neutra (carboximetil-β-CD) [75]. Além disso, devido suas cargas positivas, a tendência desses analitos é migrarem para o cátodo, local da injeção, ao passo que as CDs aniônicas migram em direção oposta, em direção ao ânodo (local de detecção).…”

Section: Análise Enantiosseletiva Da Risp Por Eletroforese Capilar Após Extração Por Hf-lpmeunclassified

Desenvolvimento de métodos cromatográficos e eletroforéticos enantiosseletivos para análise de fármacos e praguicidas em estudos de biotransformação e metabolismo in vitro

Oliveira¹

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Section: Análise Enantiosseletiva Da Risp Por Eletroforese Capilar Após Extração Por Hf-lpmeunclassified

Desenvolvimento de métodos cromatográficos e eletroforéticos enantiosseletivos para análise de fármacos e praguicidas em estudos de biotransformação e metabolismo in vitro

Oliveira¹

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Avaliação de fungos no metabolismo enantiosseletivo da Zopiclona e análise por eletroforese capilar

Albuquerque¹

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Zopiclone (ZO) is a chiral drug extensively metabolized into N-desmethylzopiclone (N-Des) and zopiclone-N-oxide (N-Ox). Pharmacological studies showed that the metabolite (S)-N-Des presents anxiolytic activity, which indicates that this metabolite has a potential to be used in the treatment of anxiety. An alternative way for obtaining this metabolite may be the biotransformation employing fungi as catalytic agent. Therefore, the aim of this study was to evaluate if fungi are able to biotransform ZO into its active metabolite N-Des and to verify if this process is enantioselective. To perform ZO and its metabolites analysis from liquid culture medium, an enantioselective method by capillary electrophoresis (CE) and dispersive liquid-liquid microextraction (DLLME) was developed. The CE analyses were carried out in 50 mmol L-1 sodium phosphate buffer pH 2.5 containing 0.5% (w/v) carboxymethyl-β-CD with a constant voltage of +25 kV and capillary temperature of 20ºC. The extraction conditions established for DLLME were: 2 mL of sample (pH adjusted using 2 mL of 0.1 mol L-1 tris-HCl buffer pH 9.5), chloroform (100 µL) and methanol (300 µL) as extraction and disperser solvent, respectively. Before the biotransformation study, the method was validated according to EMA and ANVISA guidelines for analysis of drug and metabolites in biological matrices. The method was linear over a concentration range of 90-6000 ng mL-1 for each ZO enantiomer (r > 0.999) and 50-1000 ng mL-1 for each N-Des enantiomer (r > 0.998); the absolute recovery was 52% for N-Des and 83% for ZO. Other parameters, such as: accuracy, precision, selectivity and stability were all in agreement with guideline. The developed method was employed in biotransformation studies using the following fungi: Penicillium crustosum, Aspergillus fumigatus, Nigrospora sphaerica (Sacc.) E.W. Mason, Fusarium oxysporum, Mucor rouxii, Cunninghamella elegans ATCC 10028B and Cunninghamella echinulata var elegans ATCC 8688A. Among all evaluated fungi, Cunninghamella elegans ATCC 10028B and Cunninghamella echinulata var elegans ATCC 8688A were able to biotransform the ZO to its active metabolite N-Des. Using the fungus Cunninghamella echinulata var. elegans ATCC 8688A, after 360 hours of incubation it was obtained a maximum concentration of ()-(R)-N-Des and (+)-(S)-N-Des of 508 ng mL-1 and 221 ng mL-1 , respectively with an enantiomeric excess of 39%. The fungus Cunninghamella elegans ATCC 10028B formed preferentially the metabolite (+)-(S)-N-Des. After 240 hours of incubation, the concentration of metabolites ()-(R)-N-Des and (+)-(S)-N-Des was 120 ng mL-1 and 228 ng mL-1 , respectively with enantiomeric excess of 35%.

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Coupling DLLME-CE for the Stereoselective Analysis of Venlafaxine and Its Main Metabolites after Biotransformation by Fungi

Bortoleto

Bocato

Pupo

et al. 2015

Journal of the Brazilian Chemical Society

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Capillary Electromigration Techniques for the Analysis of Drugs and Metabolites in Biological Matrices: A Critical Appraisal

Cited by 3 publications

References 94 publications

Desenvolvimento de métodos cromatográficos e eletroforéticos enantiosseletivos para análise de fármacos e praguicidas em estudos de biotransformação e metabolismo in vitro

Desenvolvimento de métodos cromatográficos e eletroforéticos enantiosseletivos para análise de fármacos e praguicidas em estudos de biotransformação e metabolismo in vitro

Avaliação de fungos no metabolismo enantiosseletivo da Zopiclona e análise por eletroforese capilar

Coupling DLLME-CE for the Stereoselective Analysis of Venlafaxine and Its Main Metabolites after Biotransformation by Fungi

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