کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7616376 | 1494038 | 2016 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Chiral analysis of carvedilol and its metabolites hydroxyphenyl carvedilol and O-desmethyl carvedilol in human plasma by liquid chromatography-tandem mass spectrometry: Application to a clinical pharmacokinetic study
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Chiral analysis of carvedilol and its metabolites hydroxyphenyl carvedilol and O-desmethyl carvedilol in human plasma by liquid chromatography-tandem mass spectrometry: Application to a clinical pharmacokinetic study Chiral analysis of carvedilol and its metabolites hydroxyphenyl carvedilol and O-desmethyl carvedilol in human plasma by liquid chromatography-tandem mass spectrometry: Application to a clinical pharmacokinetic study](/preview/png/7616376.png)
چکیده انگلیسی
Carvedilol is an antihypertensive drug, which is available in clinical practice as a racemic mixture. (S)-(â)-carvedilol is a β- and α1-adrenergic antagonist, while (R)-(+)-carvedilol only acts as an α1-adrenergic antagonist. Carvedilol is metabolized mainly by glucuronidation and, to a lesser extent, by CYP2D6 to hydroxyphenyl carvedilol (OHC) and by CYP2C9 to O-desmethyl carvedilol (DMC). This study describes the development and validation of a method for the sequential analysis of the enantiomers of carvedilol, OHC and DMC in plasma using a Chirobiotic® V chiral-phase column coupled to an LC-MS/MS system. The method was linear in the range of 0.05-100, 0.05-10 and 0.02-10 ng/mL for the carvedilol, OHC and DMC enantiomers, respectively. Application of the method to the investigation of a patient with type 2 diabetes mellitus treated with a single oral dose of 25 mg racemic carvedilol showed plasma accumulation of the (R)-(+)-carvedilol, (R)-(+)-DMC and (R)-(+)-OHC enantiomers. These results suggest that plasma accumulation of (R)-(+)-carvedilol cannot be explained by its oxidative metabolism.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography B - Volumes 1015â1016, 15 March 2016, Pages 173-180
Journal: Journal of Chromatography B - Volumes 1015â1016, 15 March 2016, Pages 173-180
نویسندگان
Glauco Henrique Balthazar Nardotto, Eduardo Barbosa Coelho, Maria Paula Marques, Vera Lucia Lanchote,