title: Analysis of carvedilol enantiomers in human plasma using chiral stationary phase column and liquid chromatography with tandem mass spectrometry.
abstract: 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.
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Josiane Cristófani
authors.initials: JC
authors.lastname: Poggi
authors.forename: Flávia Garcez
authors.initials: FG
authors.lastname: Da Silva
authors.forename: Eduardo Barbosa
authors.initials: EB
authors.lastname: Coelho
authors.forename: Maria Paula
authors.initials: MP
authors.lastname: Marques
authors.forename: Carlo
authors.initials: C
authors.lastname: Bertucci
authors.forename: Vera Lucia
authors.initials: VL
authors.lastname: Lanchote
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry* / Q000493:pharmacokinetics; D001774:Blood Chemical Analysis / Q000379:methods*; D002227:Carbazoles / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry* / Q000493:pharmacokinetics; D000077261:Carvedilol; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D057230:Limit of Detection; D011412:Propanolamines / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol