medigraphic.com
ISSN 1561-2988 (Print)

2012, Number 3

<< Back Next >>

Rev Cubana Farm 2012; 46 (3)

Assessment of bacterial endotoxins in Zoledronic acid injectable drug by using Limulus amebocyte lysate test

Burguet LN, Reyes TMI, Brito GLC, Troche CY

Language: Spanish
References: 22
Page: 320-328
PDF size: 76.93 Kb.


ABSTRACT

Objective: to asses the presence of bacterial endotoxins in Zoledronic Acid injectable drug by using the Limulus amebocyte lysate test, particularly by the gelling procedure.
Methods: the assay was performed in two tests: the first was the confirmation of labeled lysate sensitivity by preparing a standard curve with serial double dilutions of endotoxins four times, and the second was the inhibition product test in which serial double dilutions of endotoxins were prepared with apyrogenic water and with samples from the batches to be tested, without exceeding the maximum valid dilution. The end point was determined and the geometric mean was calculated. Working dilution was defined and then validated four times in three consecutive batches.
Results: the lysate sensitivity was 0.03125 EU/mL). The maximum valid dilution and the working dilution were 112 EU/mL and 1/100 EU/mL) respectively. The amount of bacterial endotoxins present in three batches of the injectable drug did not exceed the set limit, so it complied with the quality specifications for this test.
Conclusions: the standardization of the gelling method conditions makes it possible to state that this method is effective, reliable, quick and easy-to-perform, so it can be used as a regular test in the quality control of the analyzed parenteral drug.


REFERENCES

  1. The United States Pharmacopeia, USP 30. The National Formulary, NF 25. Rockville: Mack Printing; 2007.

  2. Mascoli CC, Wery ME. Limulus amebocyte lysate (LAL) test for detecting pyrogens in parenteral injectable products and medical devices: Advantages to manufacturers and regulatory officials. J Parenteral Drugs Assoc. 1979;33(2):81-95.

  3. Perdomo R. Ensayo del lisado de amebocitos del Limulus (LAL). Rev Cubana Farm. 2004;38(1):8-15

  4. Weary M, Pearson FA. Manufac turer's Guide to Depyrogenation. BioPharm. 1988 April;25:22-9.

  5. Weary ME. Understanding and setting endotoxin limits. J Parent Sci Technol. 1990;44(1):16-8.

  6. Lewn J, Bang FB. The role of endotoxin in the extracellular coagulation of limulus blood. Bull Johns Hopkins Hosp. 1964;115(1):265-70.

  7. Iwanaga, S. Primitive coagulation systems and their message to modern biology. Thrombosis Haemostasis. 1993;70(1):48-55.

  8. Novitsky TJ. Discovery to commercialization: the blood of the horseshoe crabs. Oceanus. 1991;27(1):13-8.

  9. Dawson ME. A wealth of options. Choosing a LAL test methods LAL Update. 1995;13(3):15.

  10. Associates of Cape Cod Inc. Preliminary testing. LAL Update. 1996;14(1):1-5.

  11. Dawson ME. Preliminary testing. LAL Update. 1996;14(1):1-5.

  12. Guideline on validation of the limulus amebocyte lysate test as an end product endotoxin test for human and animal parenteral Drugs. Biological products and medical devices. U.S. Department of Health and Human Services, Public Health Service, Food and Drugs Administration. January, 1983.

  13. Cooper JF. Validation of bacterial endotoxins test methods LAL Times. 1999;6(2):1-7.

  14. Carrillo C, Ospina J, Aldana D, Arias J, Escheverri C. Validación de endotoxinas bacterianas en Ranitidina y Penicilina G sódica inyectables mediante la prueba de Lisado del amebocito de Limulus. Rev. Universitas Scientiatum. 2006;11(1):15-28.

  15. Osorio O, Pérez X, Arias J, Rodríguez D, Fernández C. Interferencias en la validación del ensayo de Lisado de Amebocitos de Limulus para Oxitetraciclina 500 mg/mL Rev Cubana Farm. 2007;41(1):12-9.

  16. Morote M. Validación de la técnica L.A.L. (GEL CLOT) en los agentes de radiodiagnóstico y radioisótopos. Alasbimn J [Internet]. 2002 July [citado 13 Feb 2011];4(16). Disponible en: http://www.alasbimnjournal.cl/revistas/16/sec_b /0,1990,SCID%253D1497,00.html

  17. Weary ME. Depyrogenation. In: Pearson FC editor. Pyrogens: endotoxins, LAL testing and depyrogenation. New York: Marcel Dekker; 1985. p. 203-28.

  18. Suffredini AF, O´Grady NP. Pathophysiological responses to endotoxins in humans. En: Brade, H, Opal, SM, Vogel N, Morrison DC, editors. Endotoxin in health and disease. New York: Marcel Dekker; 2000. p. 817-30.

  19. Hochstein HD, Fizgerald EA, Mcmahon, FG, Vargas R. Properties of US Standard (EC-5) in human male volunteers. J Endotox Res. 1994;1:52-6.

  20. Cooper JF. Principles and applications of the Limulus test for pyrogen in parenteral drugs. Bull Parenteral Drug Assc. 1975;29(3):122-30.

  21. Cooper JF, Hochtein HD, Seligmann EB. The Limilus test for endotoxin (Pyrogen) in radiopharmaceutical and biological. Bull Parenter Drug Assoc. 1972;26(4):153-62.

  22. Associates of Cape Cod Inc. Routine testing and retest. LAL Update. 1997;15(2):1-4.




2020     |     www.medigraphic.com