FIXED DOSE COMBINATIONS WITH SELECTIVE BETA-BLOCKERS: QUANTITATIVE DETERMINATION IN BIOLOGICAL FLUIDS
Abstract
Hypertension is one of the most common causes of death, a complex and incompletely controlled disease for millions of patients. Metoprolol, bisoprolol, nebivolol and atenolol are selective beta-blockers frequently used in the management of arterial hypertension, alone or in fixed combination with other substances. This study presents the most used analytical methods for simultaneous determination in biological fluids of fixed combinations containing selective beta-blockers. Articles in PubMed, Science Direct and Wiley Journals databases published between years 2004-2014 were reviewed. Methods such as liquid chromatography–mass spectrometry–mass spectrometry (LC-MS/MS), high performance liquid chromatography (HPLC) or high performance liquid chromatography–mass spectrometry (HPLC-MS) were used for determination of fixed combination with beta-blockers in human plasma, rat plasma and human breast milk. LC-MS/MS method was used for simultaneous determination of fixed combinations of metoprolol with simvastatin, hydrochlorothiazide or ramipril, combinations of nebivolol and valsartan, or atenolol and amlodipine. Biological samples were processed by protein precipitation techniques or by liquid-liquid extraction. For the determination of fixed dose combinations of felodipine and metoprolol in rat plasma liquid chromatography–electrospray ionization–mass spectrometry (LC-ESI-MS/MS) was applied, using phenacetin as internal standard. HPLC-MS method was applied for the determination of bisoprolol and hydrochlorothiazide in human plasma. For the determination of atenolol and chlorthalidone from human breast milk and human plasma the HPLC method was used. The analytical methods were validated according to the specialized guidelines, and were applied to biological samples, thing that confirms the permanent concern of researchers in this field.
References
2. Saleem K, Ali I, Kulsum U, Aboul-Enein HY. Recent developments in HPLC analysis of ß-blockers in biological samples. J Chromatogr Sci 2013; 51(8): 807-818.
3. Leon MM, Mitu F. The clinical-epidemiological study of drugs used to treat arterial hypertension and comorbidities associated. Rev Med Chir Soc Med Nat Iaşi 2013; 117(2): 488-494.
4. Brujbu I, Macovei A, Murariu RV, Rădulescu M. Clinical and epidemiological assessment of the incidence of arterial hypertension in a permanent medical center. Rev Med Chir Soc Med Nat Iaşi 2014; 118(2): 471-478.
5. Panjrath GS, Messerli FH. ß-Blockers for primary prevention in hypertension: Era Bygone? Prog Cardiovasc Dis 2006; 49(2): 76-87.
6. Stanton T, Reid JL. Fixed dose combination therapy in the treatment of hypertension. J Hum Hypertens 2002; 16: 75-78.
7. Frank J. Managing Hypertension Using Combination Therapy. Am Fam Physician 2008; 77(9): 1279-1286.
8. Chang H, Li J, Li J et al. Simultaneous determination of amlodipine and bisoprolol in rat plasma by a liquid chromatography/tandem mass spectrometry method and its application in pharmacokinetic study. J Pharm Biomed Anal 2012; 71: 104-110.
9. Selvan PS, Pal TK. Chromatography – tandem mass spectrometry method for the simultaneous quan-titation of metoprolol succinate and simvastatin. J Pharm Biomed Anal 2009; 49: 780-785.
10. Sarkar AK, Ghosh D, Das A et al. Simultaneous determination of metoprolol succinate and amlodipine besylate in human plasma by liquid chromatography – tandem mass spectrometry and its application in bioequivalence study. J Chromatogr B 2008; 873: 77-85.
11. Gao F, Zhang M, Cui X, Wang Z, Sun Y, Gu J. Simultaneous quantitation of hydrochlorothiazide and metoprolol in human plasma by liquid chromatography – tandem mass spectrometry. J Pharm Biomed Anal 2010; 52: 149-154.
12. Gowda KV, Mandal U, Selvan PS et al. Liquid chromatography – tandem mass spectrometry method for simultaneous determination of metoprolol tartrate and ramipril in human plasma. J Chromatogr B 2007; 858: 13-21.
13. Kallem RR, Ramesh M, Seshagirirao JV. Validated LC-ESI-MS/MS method for simultaneous quanti-tation of felodipine and metoprolol in rat plasma: application to a pharmacokinetic study in rats. Biomed Chromatogr 2013; 27: 784-791.
14. Tutunji MF, Ibrahim HM, Khabbas MH, Tutunji LF. Simultaneous determination of bisoprolol and hydrochlorothiazide in human plasma by HPLC coupled with mass spectrometry. J Chromatogr B 2009; 877: 1689-1697.
15. Selvan PS, Gowda KV, Mandal U, Solomon WD, Pal TK. Simultaneous determination of fixed dose combination of nebivolol and valsartan in human plasma by liquid chromatographic – tandem mass spectrometry and its application to pharmacokinetic study. J Chromatogr B 2007; 858: 143-150.
16. Elgawish MS, Mostafa SM, Elshanawane AA. Simple and rapid HPLC method for simultaneous determination of atenolol and chlortalidone in spiked human plasma. Saudi Pharm J 2011; 19: 43-49.
17. Kallem RR, Inamadugu JK, Ramesh M, Seshagirirao JV. Sensitive LC-MS/MS-ESI method for sim-ultaneous determination of nifedipine and atenolol in human plasma and its application to a human pharmacokinetic study. Biomed Chromatogr 2013; 27(3): 349-355.
18. Kallem RR, Mullangi R, Hotha KK, Ravindranath LK, Spoorthy YN, Seshagirirao JV. Simultaneous estimation of amlodipine and atenolol in human plasma: a sensitive LC-MS/MS method validation and its application to a clinical PK study. Bioanalysis 2013; 5(7): 827-837.
19. El-Gindy A, Sallam S, Abdel-Salam RA. HPLC method for the simultaneous determination of atenolol and chlorthalidone in human breast milk. J Sep Sci 2008; 31: 677-682.

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