Stereoselective analysis of carvedilol in human plasma and urine using HPLC after chiral derivatization.
An enantioselective high-performance liquid chromatographic method for the analysis of carvedilol in plasma and urine was developed and validated using (-)-menthyl chloroformate (MCF) as a derivatizing reagent. Chloroform was used for extraction, and analysis was performed by HPLC on a C18 column with a fluorescence detector. The quantitation limit was 0.25 ng/ml for S(-)-carvedilol in plasma and 0.5 ng/ml for R(+)-carvedilol in plasma and for both enantiomers in urine. The method was applied to the study of enantioselectivity in the pharmacokinetics of carvedilol administered in a multiple dose regimen (25 mg/12 h) to a hypertensive elderly female patient. The data obtained demonstrated highest plasma levels for the R(+)-carvedilol (AUC(SS) (0-12) 75.64 vs 37.29 ng/ml). The enantiomeric ratio R(+)/S(-) was 2.03 for plasma and 1.49 for urine (Ae(0-12) 17.4 vs 11.7 microg).
School of Pharmaceutical Sciences, São Paulo State University Julio de Mesquita Filho, Araraquara, São Paulo, Brazil. peccinin@fcfar.unesp.br <peccinin@fcfar.unesp.br>
Rosângela G
RG
Peccinini
Valdecir F
VF
Ximenes
Evandro J
EJ
Cesarino
Vera L
VL
Lanchote
D018674:Adrenergic Antagonists / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000368:Aged; D000959:Antihypertensive Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002227:Carbazoles / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000077261:Carvedilol; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D011412:Propanolamines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D013237:Stereoisomerism
D018674:Adrenergic Antagonists; D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol