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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Neves, Daniel Valente Vieira, Carolina Pinto Coelho, Eduardo Barbosa Marques, Maria Paula Lanchote, Vera Lucia |
| Description | Country affiliation: Brazil Author Affiliation: Neves DV ( Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.) |
| Abstract | Nebivolol is available for clinical use as a racemic mixture. Isomer d-nebivolol (SRRR) is a ß1 adrenergic receptor blocker and its antipode, l-nebivolol (RSSS) is responsible for endothelium-dependent NO liberation. This report describes the development and validation of a method of analysis of nebivolol isomers in human plasma by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Nebivolol isomers were extracted from 2mL aliquots of plasma spiked with tramadol as internal standard, alkalinized and added of sodium chloride and diisopropyl ether:dichloromethane (70:30, v/v). Nebivolol isomers were resolved on a Chirobiotic(®) V column using methanol:acetic acid:diethylamine (100:0.15:0.05, v/v/v) as mobile phase. Protonated ion and respective ion product were monitored in transitions 406>151 for nebivolol and 264>58 for internal standard tramadol. There was no racemization of nebivolol isomers during the procedures of sample preparation and chromatographic analysis and matrix effect was absent. Analysis of nebivolol isomers showed linearity for plasma concentrations of 25-2500pg/mL of each isomer. The quantification limit was 25pg of each isomer/mL of plasma. Variation coefficients and inaccuracy calculated in precision and accuracy determinations were lower than 15%. Nebivolol was stable in human plasma after three successive cycles of freezing and thawing, during 4h at room temperature and after processing during 12h in the auto sampler at 5°C showing deviation values lower than 15%. The method was applied in a study of the kinetic disposition of nebivolol in plasma samples collected until 48h after administration of an oral single dose of 10mg of racemic nebivolol hydrochloride to a patient with systemic arterial hypertension. The clinical study demonstrated that the nebivolol pharmacokinetics is stereoselective. Isomer l-nebivolol showed higher AUC(0-∞) (9.4ng/h/mL vs. 4.7ng/h/mL) and smaller apparent clearance (Cl/f) (531.8L/h vs. 1304.4L/h) when compared to antipode d-nebivolol. |
| File Format | HTM / HTML |
| ISSN | 15700232 |
| Volume Number | 940 |
| e-ISSN | 1873376X |
| Journal | Journal of Chromatography B |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2013-12-01 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Analytical Chemistry Benzopyrans Blood Chromatography, High Pressure Liquid Methods Ethanolamines Tandem Mass Spectrometry Adult Chemistry Isolation & Purification Humans Isomerism Linear Models Nebivolol Reproducibility Of Results Sensitivity And Specificity Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Analytical Chemistry Clinical Biochemistry Biochemistry |
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