Rapid and Sensitive Carvedilol Assay in Human Plasma Using a High-Performance Liquid Chromatography with Mass/Mass Spectrometer Detection Employed for a Bioequivalence Study

Abstract

A method for the determination of carvedilol in human plasma was developed using a high-performance liquid chromatography with tandem mass spectrometer (HPLC-MS/MS). Plasma samples were deproteinized using acetonitrile and the supernatant was directly injected onto the HPLC column without any preparative steps. Chromatography was performed on a reversed-phase (C 18 ) column with isocratic mobile phase for 2 min. The calibration curve was linear over the range of 2 to100 ng/ml (R 2 > 0.9998) and the lower limit of quantitation (LLOQ) was 2 ng/ml. This method showed acceptable precision and accuracy, good recovery from the plasma matrix, and stability during the analytical procedures. When its application to the bioequivalence test of two carvedilol 25 mg tablet formulations in male healthy 28 volunteers, this validated analysis method was appropriate resulting in the bioequivalence of two formulations: no statistically significant difference was observed between the logarithmic transformed area under curve (AUC) and maximum plasma concentration (C max ) values of the two formulations. The 90% confidence interval for the ratio of the above mentioned two parameters were within the bioequivalence limit of 0.80-1.25. These results suggested that the HPLC-MS/MS analysis method developed was suitable for the carvedilol analysis in human plasma.

Optimization of carvedilol solid lipid nanoparticles: An approach to control the release and enhance the oral bioavailability on rabbits

“…The percent of CVD entrapped in the prepared SLNs was determined by an ultracentrifugation method as described before [ 27 , 28 ]. Briefly, the sample was centrifuged, filtered and the amount of free and entrapped CVD was dissolved in methanol and analyzed at 248 nm using the HPLC method [ 29 ]. Eq 1 was used for the calculation of the entrapment efficiency (EE %): where Fs is the amount of free CVD diffused in collection section after ultracentrifugation, and Ts is the calculated CVD concentration used in the formulation of SLNs.…”

“…At the predetermined 12 time intervals over 12 h, aliquots of 5 ml were withdrawn and immediately replenished with the fresh medium. The samples were analyzed for CVD concentration using the HPLC method after suitable dilution [ 29 ].…”

“…The blood samples (0.5 ml) were withdrawn from the marginal ear vein at predetermined time points (0, 0.5, 1, 2, 4, 6, 8, 12, and 24 h) after oral administration of the test/reference formulations. Afterward, the samples were centrifuged at 3,500 rpm for 5 min and then the obtained plasma samples were stored at −20°C until assay using the previously reported modified HPLC method [ 29 , 31 ].…”

Development and optimization of carvedilol orodispersible tablets: enhancement of pharmacokinetic parameters in rabbits

“…Determination of CVD in plasma was done using a modified HPLC method. 25 An Agilent 1200 series HPLC apparatus (Agilent, Waldbronn, Germany) was used with a tandem mass spectrometry detector system. The mobile phase was a mixture of acetonitrile and 0.1% formic acid (70:30, v/v) at a flow rate of 0.25 mL per minute.…”

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“…Chemically CP is (2RS)-1-(9H-Carbazol- 4 Several analytical techniques are available for estimation of Carvedilol Phosphate in bulk dosage form by HPLC, HPTLC and UV Spectrophotometric method [4][5][6][7][8][9][10][11][12][13][14] . Keeping this objective in mind an attempt has been made to develop and validate the HPLC-fluorescence method for the analysis of Carvedilol Phosphate which would be highly sensitive, having good resolution and reproducible.…”