Analysis of carvedilol enantiomers in human plasma using chiral stationary phase column and liquid chromatography with tandem mass spectrometry
| Autor: | Vera Lucia Lanchote, Eduardo Barbosa Coelho, Maria Paula Marques, Flávia Garcez Da Silva, Carlo Bertucci, Josiane Cristófani Poggi |
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| Přispěvatelé: | Poggi JC, Da Silva FG, Coelho EB, Marques MP, Bertucci C, Lanchote VL |
| Rok vydání: | 2012 |
| Předmět: |
Adult
PHARMACOKINETICS ENANTIOMERS Carbazoles Administration Oral Tandem mass spectrometry Catalysis Analytical Chemistry Propanolamines chemistry.chemical_compound Pharmacokinetics Limit of Detection Tandem Mass Spectrometry Drug Discovery medicine Diisopropyl ether Humans LC-MS/MS Carvedilol Spectroscopy Antihypertensive Agents Pharmacology Detection limit Chromatography Chemistry Organic Chemistry Reproducibility of Results Stereoisomerism ESPECTROMETRIA DE MASSAS CHIRAL STATIONARY PHASE Chiral column chromatography Hypertension Racemic mixture Enantiomer Blood Chemical Analysis medicine.drug Chromatography Liquid |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Carvedilol is an antihypertensive drug available as a racemic mixture. (-)-(S)-carvedilol is responsible for the nonselective β-blocker activity but both enantiomers present similar activity on α(1) -adrenergic receptor. To our knowledge, this is the first study of carvedilol enantiomers in human plasma using a chiral stationary phase column and liquid chromatography with tandem mass spectrometry. The method involves plasma extraction with diisopropyl ether using metoprolol as internal standard and direct separation of the carvedilol enantiomers on a Chirobiotic T® (Teicoplanin) column. Protonated ions [M + H](+) and their respective ion products were monitored at transitions of 407 > 100 for the carvedilol enantiomers and 268 > 116 for the internal standard. The quantification limit was 0.2 ng ml(-1) for both enantiomers in plasma. The method was applied to study enantioselectivity in the pharmacokinetics of carvedilol administered as a single dose of 25 mg to a hypertensive patient. The results showed a higher plasma concentration of (+)-(R)-carvedilol (AUC(0-∞) 205.52 vs. 82.61 (ng h) ml(-1) ), with an enantiomer ratio of 2.48. |
| Databáze: | OpenAIRE |
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