Titre du document / Document title

Fast screening method for the determination of angiotensin II receptor antagonists in human plasma by high-performance liquid chromatography with fluorimetric detection

Auteur(s) / Author(s)

GONZALEZ L. ⁽¹⁾ ; LOPEZ J. A. ⁽¹⁾ ; ALONSO R. M. ⁽¹⁾ ; JIMENEZ R. M. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Departamento de Química Analítica, Facultad de Ciencias, Universidad del País Vasco, Apdo, 644, 48080 Bilbao, ESPAGNE

Résumé / Abstract

A selective, accurate and precise high-performance liquid chromatographic assay coupled to fluorescence detection was developed for the detection of some angiotensin II receptor antagonists (ARA II): Losartan, Irbesartan, Valsartan, Candesartan cilexetil and its metabolite Candesartan M1. The analytes and the internal standard (bumetanide, a high-ceiling diuretic) were extracted from plasma under acidic conditions by means of solid-phase extraction using C₈ cartridges. This procedure allowed recoveries close to 80% for all these drugs excluding Candesartan cilexetil (70%) which presented adsorption processes on glass and plastic walls. The analytes and potential interferences were separated on a reversed-phase column, μBondapak C₁₈, at room temperature. A gradient elution mode was used to carry out the separation, the optimal mobile phase being composed of acetonitrile-5 mM acetate buffer, pH 4, at variable flow-rates (from 1.0 to 1.2 ml/min). Fluorescence detector was set at an excitation wavelength of 250 nm and an emission wavelength of 375 nm. Intra- and inter-day relative standard deviations for all the compounds were lower than 8% except for Losartan (12%) and the method assesses a quite good accuracy (percentage of relative error -6% in most of the cases). The limit of quantitation for these compounds was 3 ng/ml for Candesartan cilexetil and M1, 16 ng/ml for Losartan and 50 ng/ml for Irbesartan and Valsartan, which allows their determination at expected plasma concentration levels. This assay method has been successfully applied to plasma samples obtained from hypertensive patients under clinical studies after oral administration of a therapeutic dose of some of these ARA II compounds.

Revue / Journal Title

Journal of chromatography   ISSN 0021-9673   CODEN JOCRAM 

Source / Source

Congrès
International Symposium on High Performance Liquid Phase Separations and Related Techniques N^o25, Maastricht , PAYS-BAS (17/06/2001)
2002, vol. 949, n^o 1-2 (377 p.)  (32 ref.), [Notes: Part II], pp. 49-60

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1958) (Revue)

Mots-clés anglais / English Keywords

Cardiovascular disease ; Hypertension ; Validation ; Elution ; Gradient ; Fluorescence detector ; Reversed phase chromatography ; HPLC chromatography ; Solid phase extraction ; Sample preparation ; Pharmacokinetics ; Oral administration ; Patient ; Human ; Blood ; Blood plasma ; Biological fluid ; Non peptide compound ; α-Aminoacid ; Biphenyl derivatives ; Tetrazole derivatives ; Benzimidazole derivatives ; Antihypertensive agent ; AT1 angiotensin receptor ; Angiotensin II ; Antagonist ; Angiotensin antagonist ; Metabolite ; Cilexetil ; Candesartan ; Valsartan ; Irbesartan ; Losartan ; Quantitative analysis ; Chemical analysis ;

Mots-clés français / French Keywords

Appareil circulatoire pathologie ; Sartan ; Valine dérivé ; Hypertension artérielle ; Validation ; Elution ; Gradient ; Détecteur fluorescence ; Chromatographie phase inverse ; Chromatographie HPLC ; Extraction SPE ; Préparation échantillon ; Pharmacocinétique ; Voie orale ; Malade ; Homme ; Sang ; Plasma sanguin ; Liquide biologique ; Composé non peptide ; α-Aminoacide ; Biphényle dérivé ; Tétrazole dérivé ; Benzimidazole dérivé ; Antihypertenseur ; Récepteur angiotensine AT1 ; Angiotensine II ; Antagoniste ; Antagoniste angiotensine ; Métabolite ; Cilexétil ; Candésartan ; Valsartan ; Irbésartan ; Losartan ; Analyse quantitative ; Analyse chimique ;

Mots-clés espagnols / Spanish Keywords

Aparato circulatorio patología ; Hipertensión arterial ; Validación ; Elución ; Gradiente ; Detector fluorescencia ; Cromatografía fase inversa ; Cromatografía HPLC ; Extracción SPE ; Preparación muestreo ; Farmacocinética ; Vía oral ; Enfermo ; Hombre ; Sangre ; Plasma sanguíneo ; Líquido biológico ; Compuesto no péptido ; α-Aminoácido ; Bifenilo derivado ; Tetrazol derivado ; Benzimidazol derivado ; Antihipertensivo ; Receptor angiotensina AT1 ; Angiotensina II ; Antagonista ; Antagonista angiotensina ; Metabolito ; Cilexetilo ; Candesartán ; Valsartán ; Irbesartán ; Losartán ; Análisis cuantitativo ; Análisis químico ;

Localisation / Location

INIST-CNRS, Cote INIST : 8577 A, 35400010237882.0060