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AAPS PharmSci

, 5:116 | Cite as

Atenolol quantification in human plasma by high-performance liquid chromatography: Application to bioequivalence study

  • Luis Renato Pires de AbreuEmail author
  • Silvana Aparecida Calafatti de Castro
  • José Pedrazzoli
Article

Abstract

An accurate, precise, and sensitive high-performance liquid chromatography (HPLC) assay was developed for the determination of atenolol in human plasma samples to compare the bioavailability of 2 atenolol tablet (50 mg) formulations in 24 volunteers of both sexes. The study had an open, randomized, 2-period crossover design with a 1-week washout period. Plasma samples were obtained over a 24-hour interval. Atenolol concentrations were analyzed by combined reversed phase liquid chromatography and fluorescence detection (λEX = 258 nm, λEM = 300 nm). From the atenolol plasma concentration versus time curves, the following pharmacokinetic parameters were obtained: AUC0–24h, AUC0–∞, and Cmax. The geometric mean of test/reference 50-mg tablets individual percent ratio was 102.2% for AUC0–24h, and 101.6% for Cmax. The 90% confidence intervals (CI) were 100.2% to 105.4% and 100.9% to 103.5%, respectively. Since the 90% CI for both Cmax and AUC0–24h were within the 80% to 125% interval proposed by the Food and Drug Administration, it was concluded that atenolol (50-mg tablets) test formulation was bioequivalent to the reference formulation, with regard to both the rate and extent of absorption.

Keywords

atenolol bioequivalence HPLC plasma determination 

References

  1. 1.
    Clementi WA, Garvey TQ, Clifton GD, McCoy RA, Brandt S, Schwartz S. Single dose pharmacokinetics of (S)-atenolol administered orally as a single enantiomer formulation and as a racemic mixture (Tenormin). Chirality. 1994;6(3):169–174.PubMedCrossRefGoogle Scholar
  2. 2.
    Egginger G, Lindner W, Karh S, Stoschitzky K. Stereoselective HPLC bioanalysis of atenolol enantiomers in plasma: application to a comparative human pharmacokinetic study. Chirality. 1993;5: 506–512.CrossRefGoogle Scholar
  3. 3.
    Physicians Desk Reference-PDR, 51st ed, Montvale, NJ: Medical Economics Company, Inc; 1999:1548.Google Scholar
  4. 4.
    Cruickshank JM, McAinsh J. Atenolol and ischemic heart disease: an overview. Curr Med Res Opin. 1991;12:485–496.PubMedCrossRefGoogle Scholar
  5. 5.
    Wadworth AN, Murdoch D, Brogden RN. Atenolol: a reappraisal of its pharmacological properties and therapeutic use in cardiovascular disorders. Drugs. 1991;42:468–510.PubMedCrossRefGoogle Scholar
  6. 6.
    Psaty BM, Koepsell TD, LoGerfo JP, et al. Beta-blockers and primary prevention of coronary heart disease in patients with high blood pressure. JAMA. 1989;261:2087–2094.PubMedCrossRefGoogle Scholar
  7. 7.
    Heel RC, Brogden RN, Speight TM, Avery GS. Atenolol: a review of its pharmacological properties and therapeutic efficacy in angina pectoris and hypertension. Drugs. 1979;17:425–460.PubMedCrossRefGoogle Scholar
  8. 8.
    Majid PA, van der Vijgh WJF, Wadeh R, van der Wall EF, Roos JP. Once daily atenolol (Tenormine) in the treatment of angina pectoris. Eur J Cardiol. 1979;9(6):419–35.PubMedGoogle Scholar
  9. 9.
    Sitzler G, Heibel B, Lucker PW, Palm D. Bioequivalence of two atenolol formulations in healthy volunteers. Evaluation and prediction of effect kinetics at β-adrenoceptors in vivo by means of a radioreceptor assay. Methods Find Exp Clin Pharmacol. 1991;13(2):129–137.PubMedGoogle Scholar
  10. 10.
    Yee YG, Ruben P, Blaschke TF. Atenolol determination by high-performance liquid chromatography and fluorescence detection. J Chromatogr. 1993;171:357–362.CrossRefGoogle Scholar
  11. 11.
    Shen J, Wanwimolruk S, Hung CT, Zoest AR. Quantitative analysis of beta-blockers in human plasma by reversed-phase ion-pair high-performance liquid chromatography using a micropore column. J Liq chromatogr. 1991;14:777–793.CrossRefGoogle Scholar
  12. 12.
    Terry S, Teitelbaum Z. A liquid chromatographic method for determination of atenolol in human plasma. J Liq Chromatogr. 1991;1:3735–3744.Google Scholar
  13. 13.
    Martins ML, Pierossi MA, Moraes LA, et al. Comparative bioavailability of two atenolol tablet formulations after a single dose administration. Int J Clin Pharm Ther. 1997;35(8):324–328.Google Scholar
  14. 14.
    Marzo A, Monti NC, Dal Bo L, et al. Comparative bioavailability of two formulations containing atenolol and chlortalidone associated in a 4∶1 fixed combination. Arzneimittelforschung. 2000;50(9):802–808.PubMedGoogle Scholar
  15. 15.
    Li J, Anari R, Kwok D. Rapid and simultaneous analysis of seven beta-blockers in human plasma using electrospray LC/MS/MS. AAPS 02 PharmSci. 1999;1(4). Abstract 2854. 0266 0137 VGoogle Scholar
  16. 16.
    Food and Drug Administration. Bioavailability and bioequivalence requirements. Fed Regist. 1985;320:154–173.Google Scholar
  17. 17.
    Food and Drug Administration. Bioavailability and bioequivalence requirements; abbreviated applications; proposed revisions. Proposed rule. Fed Regist. 1998;63:64222–64228.Google Scholar
  18. 18.
    Food and Drug Administration. Guidance for industry, bioanalytical methods validation for human studies. Food and Drug Administration Web site. Available at: http://www.fda.gov./cder/guidance/,1998b. August/1998.Google Scholar
  19. 19.
    Food and Drug Administration. In vivo bioequivalence guidances. Pharmacopeial Forum. 1993;19:6501–6508.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2003

Authors and Affiliations

  • Luis Renato Pires de Abreu
    • 1
    Email author
  • Silvana Aparecida Calafatti de Castro
    • 2
  • José Pedrazzoli
    • 2
  1. 1.Department of PharmacologyFaculty of Medical Sciences-UNICAMPCampinasBrazil
  2. 2.Integrated Unit of Pharmacology and Gastroenterology-São FranciscoUniversity Medical SchoolBragança PaulistaBrazil

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