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

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DOI: 10.4236/ajac.2010.13017   PDF   HTML     5,894 Downloads   11,777 Views   Citations

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 (C18) column with isocratic mobile phase for 2 min. The calibration curve was linear over the range of 2 to100 ng/ml (R2 > 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 (Cmax) 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.

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S. Kim, S. Lee and H. Lee, "Rapid and Sensitive Carvedilol Assay in Human Plasma Using a High-Performance Liquid Chromatography with Mass/Mass Spectrometer Detection Employed for a Bioequivalence Study," American Journal of Analytical Chemistry, Vol. 1 No. 3, 2010, pp. 135-143. doi: 10.4236/ajac.2010.13017.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] F. Varin, L. X. Cubeddu and J. R. Powell, “Liquid Chromatographic Assay and Disposition of Carvedilol in Healthy Volunteers,” Journal of Pharmaceutical Sciences, Vol. 75, No. 12, 1986, pp. 1195-1197.
[2] E. J. Eisenberg, W. R. Patterson and G. C. Khan, “High-Performance Liquid Chromatographic Method for the Simultaneous Determination of the Enantiomers of Carvedilol and Its O-Desmethyl Metabolite in Human Plasma after Chiral Derivatization,” Journal of Chromatography B, Vol. 493, No. 1, 1989, pp. 105-115.
[3] G. M. Keating and B. Jarvis, “Carvedilol: A Review of Its Use in Chronic Heart Failure,” Drugs, Vol. 63, No. 16, 2003, pp. 1697-1741.
[4] T. W. Gehr, D. M. Tenero, D. A. Boyle, Y. Qian, D. A. Sica and N. H. Shusterman, “The Pharmacokinetics of Carvedilol and Its Metabolites after Single and Multiple Dose Oral Administration in Patients with Hypertension and Renal Insufficiency,” European Journal of Clinical Pharmacology, Vol. 55, No. 4, 1999, pp. 269-277.
[5] R. R. Ruffolo, M. Gellai, J. P. Heible, R. N. Willette and A. J. Nicholas, “Hemodynamic Differences between Carvedilol and Labetalol in the Cutaneous Circulation,” European Journal of Clinical Pharmacology, Vol. 38, No. (Suppl)2, 1990, pp. S112-S114.
[6] N. Hokama, N. Hobara, H. Kameya, S. Ohshiro and M. Sakanashi, “Rapid and Simple Micro-Determination of Carvedilol in Rat Plasma by High-Performance Liquid Chromatography,” Journal of Chromatography B, Vol. 732, No. 1, 1999, pp. 233-238.
[7] F. Behn, S. L?er and H. Scholz, “Determination of Carvedilol in Human Cardiac Tissue by High Performance Liquid Hromatography,” Journal of Chromatogra- phic Science, Vol. 39, No. 3, 2001, pp. 121-124.
[8] P. Ptacek, J. Macek and J. Klima, “Liquid Chromatographic Determination of Carvedilol in Human Plasma,” Journal of Chromatography B, Vol. 789, No. 2, 2003, pp. 405-410.
[9] L. Clohs and K. M. McErlane, “Comparison between Capillary Electrophoresis and High-Performance Liquid Chromatography for the Stereoselective Analysis of Carvedilol in Serum,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 31, No. 3, 2003, pp. 407-412.
[10] M. Saito, J. Kawana, T. Ohno, M. Kanako, K. Mihara, K. Hanada, R. Sugita, N. Okada, S. Osato, M. Nagayama. T. Sumiyoshi and H. Ogata, “Enantioselective and Highly Sensitive Determination of Carvedilol in Human Plasma and Whole Blood after Administration of the Racemate Using Normal-Phase High-Performance Liquid Chromatography,” Journal of Chromatography B, Vol. 843, No. 1, 2006, pp. 73-77.
[11] A. Medvedovici, F. Albu, C. Georgita, D. I. Sora, T. Galaon, S. Udrescu and V. David, “Achiral-Chiral LC/ LC-FLD Coupling for Determination of Carvedilol in Plasma Samples for Bioequivalence Purposes,” Journal of Chromatography B, Vol. 850, No. 1-2, 2007, pp. 327-335.
[12] M. Machida, M. Watanabe, S. Takechi, S. Kakinoki and A. Nomura, “Measurement of Carvedilol in Plasma by High-Performance Liquid Chromatography with Electrochemical Detection,” Journal of Chromatography B, Vol. 798, No. 2, 2003, pp. 187-191.
[13] M. Gergov, J. N. Robson, E. Duchoslav and I. Ojanper?, “Automated Liquid Chromatographic/Tandem Mass Spec- trometric Method for Screening β-Blocking Drugs in Urine,” Journal of Mass Spectrometry, Vol. 35, No. 7, 2000, pp. 912-918.
[14] E. Yang, S. Wang, J. Kratz and M. J. Cyronak, “Stereoselective Analysis Carvedilol in Human Plasma Using HPLC/MS/MS after Chiral Derivatization,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 36, No. 3, 2004, pp. 609-615.
[15] N. C. do C. Borges, G. D. Medes, D. O. Silva, V. M. Rezende, R. E. Barrientos-Astigarraga and G. D. Nucci, “Quantification of Carvedilol in Human Plasma by High-Performance Liquid Chromatography Coupled to Electrospray Tandem Mass Spectrometry: Application to Bioequivalence Study,” Journal of Chromatography B, Vol. 822, No. 1-2, 2005, pp. 253-262.
[16] D. W. Jeong, Y. H. Kim, H. Y. Ji, Y. S. Youn, K. C. Lee and H. S. Lee, “Analysis of Carvedilol in Human Plasma Using Hydrophilic Interaction Liquid Chromatography with Tandem Mass Spectrometry,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 44, No. 2, 2007, pp. 547-552.
[17] L. Clohs and K. M. McEralne, “Development of a Capillary Electrophoresis Assay for the Determination of Carvedilol Enantiomers in Serum Using Cyclodextrins,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 24, No. 4, 2001, pp. 545-554.
[18] S. W. Myung and C. H. Jo, “Gas Chromatograph-Mass Spectrometric Method for the Determination of Carvedilol and Its Metabolites in Human,” Journal of Chromatography B, Vol. 822, No. 1-2, 2005, pp. 70-77.
[19] Korea Food & Drug Administration, “Guidance Document for Bioequivalence Study,” 2008. http://betest.kfda. go.kr/country/country01.php?p=1
[20] DHHS-FDA, “Guidance for Industy-Bioanalytical Method Validation,” US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Veterinary Medicine, Rockville, May 2001. http://www.fda.gov/cder/guidance/ index.htm
[21] D. Tenero, S. Boike, D. Boyle, B. Ilson, H. F. Fesniak, S. Brozena and D. Jorkasky, “Steady-State Pharmacokinetics of Carvedilol and Its Enantiomers in Patients with Congestive Heart Failure,” Journal of Clinical Pharmacology, Vol. 40, No. 8, 2000, pp. 844-853.

  
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