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  • Title: Enantioselective and sensitive determination of carvedilol in human plasma using chiral stationary-phase column and reverse-phase liquid chromatography with tandem mass spectrometry.
    Author: Jiang J, Tian L, Huang Y, Yan Y, Li Y.
    Journal: J Chromatogr B Analyt Technol Biomed Life Sci; 2014 Jun 01; 960():92-7. PubMed ID: 24792533.
    Abstract:
    A liquid chromatography-tandem mass spectrometry method to quantify carvedilol enantiomers in human plasma was developed and validated as a measure of compliance in clinical research. Carvedilol enantiomers were extracted from human serum (0.5 mL) via liquid-liquid extraction with methyl tert-butyl ether (2.5 mL). Carvedilol-related compound C served as the internal standard. The analyte and internal standard were separated on a Sino-Chiral AD column (150 × 4.6mm, 5 μm, amylose tris-3,5-dimethylphenylcarbamate coated on silica-gel) using isocratic elution with mobile phases of methanol, water and diethylamine (94:6:0.01, v/v). The total run-time was 10.5 min. Carvedilol enantiomers were quantified using a triple quadrupole mass spectrometer operated in multiple-reaction-monitoring mode using positive electrospray ionisation. The mass transitions monitored for quantitation were carvedilol (m/z 407→222) and carvedilol-related compound C (m/z 497→222). The limits of quantification for the S- and R-carvedilol enantiomers in plasma were both 0.08 ng/mL. The method was validated in the linear range of 0.08-50 ng/mL with acceptable inter- and intra-assay precision and accuracy and stability suitable for routine laboratory practice. The method was successfully applied to samples taken from research volunteers treated with carvedilol sustained-release tablet 18 mg. Cmax and AUClast were 9.1 ± 5.1 ng/mL and 59.4 ± 39.6 ng h/mL for R-carvedilol, 4.0 ± 2.3 ng/mL and 24.7 ±15.0 ng h/mL for S-carvedilol, respectively. tmax and t1/2 were 4.6 ± 1.9h and 9.6 ± 4.5h for R-carvedilol, and 4.7 ± 1.0 h and 10.7 ± 5.7 h, respectively.
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