Simultaneous determination of omeprazole, hydroxyomeprazole and omeprazole sulphone in human plasma by isocratic HPLC-DAD: application to the phenotyping of CYP2C19 and CYP3A4 in brazilian volunteers

Linden, Rafael; Ziulkoski, Ana Luíza; Wingert, Maína; Tonello, Paula; Souto, André A.

doi:10.1590/s0103-50532007000400011

Cited by 10 publications

(9 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Plasma concentrations of OME and HOME were determined by high-performance liquid chromatography (HPLC), as described by Linden et al (2007). Briefly, to a 1 mL plasma sample, Tris buffer pH 9.5 and internal standard sulpiride (IS) were added, followed by ethyl acetate extraction.…”

Section: Determination Of Omeprazole and Hydroxyomeprazole Plasma Levelsmentioning

confidence: 99%

See 1 more Smart Citation

Relation between CYP2C19 phenotype and genotype in a group of Brazilian volunteers

Linden

Ziulkoski

Tonello

et al. 2009

Braz. J. Pharm. Sci.

Self Cite

View full text Add to dashboard Cite

The CYP2C19 gene presents polymorphism affecting the pharmacokinetics of several drugs of clinical importance. The purpose of this study was to investigate the correlation between CYP2C19 genotype and metabolic phenotype in a group of 38 Brazilian volunteers, evaluating the phenotype prediction capacity of the genotyping procedure. For CYP2C19 phenotyping, omeprazole was used as the probe drug, using the hydroxylation metabolic ratio as the phenotypic indicator. Venous blood samples were drawn before and three hours after an oral administration of 20 mg omeprazole. The plasma concentrations of omeprazole and hydroxy-omeprazole were determined by high performance liquid chromatography. The genotyping assay was carried out using a Real-Time-PCR-based assay, identifying the alleles *1 (completely functional), *2, *3 and *4 (null). The phenotyping procedure estimated the presence of 4 poor, 34 extensive and 1 ultra-extensive metabolizer. The genotyping identified 4 poor, 23 extensive and 11 intensive metabolizers. The groups of volunteers classified according to the number of active alleles of CYP2C19 had significant differences in the metabolic ratios of omeprazole hydroxylation. However, volunteers exhibiting the same number of active alleles presented different phenotypes. Therefore, the phenotyping of CYP2C19 is a more promising alternative to dose individualization of CYP2C19 substrate drugs.Uniterms: Metabolic phenotyping. Metabolic genotyping. CYP2C19 gene.O gene CYP2C19 apresenta polimorfismo genético, com impacto importante na farmacocinética de diversos fármacos de importância clínica. O objetivo deste estudo foi avaliar a correlação entre genótipo e fenótipo de CYP2C19 em um grupo de 38 voluntários brasileiros, avaliando a capacidade de predição do fenótipo a partir de testes de genotipagem. Para a fenotipagem, utilizou-se omeprazol (OME) como fármaco-sonda para CYP2C19, empregando sua razão metabólica de hidroxilação como indicador fenotípico. Amostras de sangue foram coletadas antes e três horas após a administração oral de 20mg do fármaco. As concentrações plasmáticas de OME e seu metabólito foram determinadas por cromatografia líquida de alta eficiência. A genotipagem de CYP2C19 foi realizada através de ensaio baseado na reação em cadeia da polimerase em tempo real, identificando os alelos *1 (completamente funcional),*2 e *3 (nulos). Pela fenotipagem foi possível estimar a presença de 3 metabolizadores lentos, 34 rápidos e 1 ultra-rápido; enquanto pela genotipagem foi determinada a presença de 4 metabolizadores lentos, 23 rápidos e 11 intermediários. Os grupos de voluntários classificados de acordo com o número de alelos ativos apresentaram diferenças significativas entre as razões metabólicas de hidroxilação de omeprazol. Entretanto, indivíduos com o mesmo genótipo apresentaram fenótipos diferentes. Desta forma, a fenotipagem apresenta-se como alternativa mais promissora para a individualização das doses de fármacos substratos de CYP2C19.Unitermos: Fenotipagem metabólica. Genotipagem metabólica. Gen...

show abstract

Section: Determination Of Omeprazole and Hydroxyomeprazole Plasma Levelsmentioning

confidence: 99%

“…The phenotypes are classified using metabolic ratios of OME hydroxylation, calculated with OME and HOME plasma concentrations 3 hours after a single oral administration of 20 mg OME (Linden et al, 2007). This indicator is named metabolic ratio (MR) and usually presents a normal distribution on tested populations (Tamminga et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Relation between CYP2C19 phenotype and genotype in a group of Brazilian volunteers

Linden

Ziulkoski

Tonello

et al. 2009

Braz. J. Pharm. Sci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The literature survey reveals several analytical methods for quantitative estimation of OMP alone in body fluids and in pharmaceutical formulations these methods include spectrophotometry [3][4][5][6][7][8][9][10][11][12][13][14], electrochemical methods [15], HPLC [16][17][18][19][20][21], liquid chromatography-electrospray ionization tandem mass spectrometry [22] and electrophoresis [23]. Tinidazole was estimated in body fluids and in pharmaceutical formulations by spectrophotometry [24][25][26][27][28][29], potentiometry [29], HPLC methods [29][30][31], polarography [32,33] and resonance light scattering technique [34].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Determination of Omeprazole, Tinidazole and Clarithromycin in Bulk Powder and Helicure Tablets by HPLC

Ahmed¹

2014

J Chromat Separation Techniq

View full text Add to dashboard Cite

Sensitive and precise chromatographic method was developed and validated for simultaneous determination of omeprazole (OMP), tinidazole (TND) and clarithromycin (CLR) in bulk powder, laboratory prepared mixture and pharmaceutical preparation. The technique adopted for quantification is HPLC. A mixture of acetonitrile, methanol, phosphate buffer at pH 3.5 (33: 17: 50, v/v/v) was used as a mobile phase. The stationary phase used was (150 mm×4.6 mm, 10µm) C8 LichrosorbTM analytical column. The method was linear in the range of 0.2-250 µg mL -1 , 0.5-250 µg mL -1 and 75-2000 µg mL -1 for OMP, TND and CLR respectively. The selectivity of the proposed method was checked using laboratory prepared mixtures. The proposed method was successfully applied to the analysis of OMP, TND and CLR in their mixture and in pharmaceutical dosage form without interference from other additives.

show abstract

“…Older methods were extensively reviewed by Bosch et al 5 For the analysis of OMZ and its metabolites in biological matrices, HPLC has been the technique most employed. [5][6][7][8][9][10][11][12][13] Although these methods are quite suitable for the analysis of OMZ and its metabolites in biological matrices, all of them are characterized by relatively long analysis time. Recently, we studied the highspeed analysis of OMZ in pharmaceutical formulations using a monolithic column.…”

Section: Introductionmentioning

confidence: 99%

Fast HPLC analysis of omeprazole, 5-hydroxyomeprazole and omeprazole sulfone in liquid culture medium using a monolithic column for application in biotransformation studies with fungi

Borges¹,

Durán-Patrón²,

Sánchez³

et al. 2011

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

Um método rápido por cromatografia líquida foi desenvolvido para a determinação simultânea de omeprazol (OMZ), 5-hidroxiomeprazol (5-HOMZ) e omeprazol sulfona (OMZ SUL) em meio de cultura líquido, para aplicação em estudos de biotransformação empregando fungos fitopatogênicos e endofíticos. A separação foi realizada empregando uma coluna monolítica Chromolith Fast gradient RP 18 com a fase móvel constituída por ácido trifluoroacético (TFA) 0,15% (v/v) em água (solvente A) e TFA 0,15% (v/v) em acetonitrila (solvente B). Foi empregado um gradiente linear de 5 a 90% de B em 1 minuto, vazão de 1,0 mL min -1 , temperatura de 30 ºC e detecção em 220 nm. A extração líquido-líquido foi empregada na preparação das amostras, com recuperações na faixa de 62,3-76,6% para todos os analitos. O método foi linear na faixa de 0,2-10,0 µg mL -1 (r ≥ 0,995). Os valores de precisão e exatidão intra-e inter-dias (coeficiente de variação e erro relativo) foram inferiores a 15% para todos os analitos. O método validado foi utilizado para avaliar a biotransformação do OMZ em seus principais metabólitos humanos pelos fungos selecionados. Em geral, os fungos fitopatogênicos foram mais eficientes para biotransformar o OMZ. A reação de sulfonação foi mais prevalente em todos os fungos estudados.A fast liquid chromatography method was developed and validated for the simultaneous determination of omeprazole (OMZ), 5-hydroxyomeprazole (5-HOMZ) and omeprazole sulphone (OMZ SUL) in liquid culture medium for application in biotransformation studies employing phytopathogenic and endophytic fungi. The separation was achieved using a monolithic Chromolith Fast gradient RP 18 endcapped column, using a mobile phase consisting of 0.15% (v/v) trifluoroacetid acid (TFA) in water (solvent A) and 0.15% (v/v) TFA in acetonitrile (solvent B), under linear gradient of 5 to 90% of B in 1 min, flow rate of 1.0 mL min -1 , temperature at 30 ºC and detection at 220 nm. Sample preparation was performed by liquid-liquid extraction, with recoveries in the range of 62.3 to 76.6% for all analytes. The method was linear in the range of 0.2 to 10.0 µg mL -1 (r ≥ 0.995). The values for intra-and inter-day precision (% coefficient of variation) and accuracy (% relative error) were < 15% for all analytes. The validated method was used to evaluate OMZ biotransformation to their mammalian metabolites by selected fungi. In general, the phytopathogenic fungi studied were more efficient to biotransform OMZ. The sulfonation reaction was more prevalent for all studied fungi.

show abstract

Simultaneous determination of omeprazole, hydroxyomeprazole and omeprazole sulphone in human plasma by isocratic HPLC-DAD: application to the phenotyping of CYP2C19 and CYP3A4 in brazilian volunteers

Cited by 10 publications

References 20 publications

Relation between CYP2C19 phenotype and genotype in a group of Brazilian volunteers

Relation between CYP2C19 phenotype and genotype in a group of Brazilian volunteers

Simultaneous Determination of Omeprazole, Tinidazole and Clarithromycin in Bulk Powder and Helicure Tablets by HPLC

Fast HPLC analysis of omeprazole, 5-hydroxyomeprazole and omeprazole sulfone in liquid culture medium using a monolithic column for application in biotransformation studies with fungi

Contact Info

Product

Resources

About