Validation of the method for determination of prekallikrein activator in Human Albumin

Prekallikrein activator (PKA) is regarded as one of the most important factors determining the safety of blood products such as albumin and intravenous immunoglobulin. PKA impurity at a high concentration may cause undesired side effects when administered to patients of blood products. According to requirements of the State Pharmacopoeia of the Russian Federation (13th edition) human albumin preparations have to pass test for the quantitative determination of prekallikrein activator (PKA), but there is no description of the method. The purpose of this study consisted in validation of a method of the quantitative definition of PKA in the preparations Albumin (human albumin) solution for infusions 10 % and 20 % with use of the commercial kit PreKallikrein Activator Assay Kit PW301EP («Pathway Diagnostics Ltd», UK). It is established that the method is accurate, linear, high-precision and specific. The method is characterized by the simplicity of the experiment, high accuracy and reproducibility that can be used in terms of control and analytical laboratories. It is shown that in all investigated batches of the drug Albumin (human albumin) solution for infusion 10 % and 20 % PKA content was less than 1 IU/ml, which corresponds to the requirements of the State Pharmacopoeia of the Russian Federation to these drugs.

альбумин, активатор прекалликреина, валидация, метрологические характеристики, препараты крови, albumin, prekallikrein activator (PKA), validation, the metrological characteristics, blood products

1. Kuwahara SS. Prekallikrein Activator (Hageman Factor Fragment) In Human Plasma Fractions. Transfusion 1980; 20: 433–9.

2. Geltser BI, Zhilkova NN. The activity of the kallikrein-kinin system in patients with vitamin B12 is-deficiency anemia. Bulletin SB RAMS 2005; 117: 131–4 (in Russian).

3. Aubakirova AK. Assessment of the kallikrein-kinin blood system in preterm infants with perinatal asphyxia. Herald KRSU 2010; 10: 105–11 (in Russian).

4. Cyr M, Eastlund T, Blais Ch, Rouleau J, Adam A. Bradykinin metabolism and hypotensive transfusion reactions. Transfusion 2001; 41: 136–50.

5. Nezlin R. Interactions between immunoglobulin G molecules. Immunology Letters 2010; 132: 1–5.

6. WHO. Expert committee on biological standardization. WHO Technical Report Series 1985. ¹ 725. Ð. 18.

7. Seifner A, Beck G, Bayer P, Eichmeir S, Lackner F, Rögelsperger O, et al. Assessment of immunoglobulin concentrates on thrombogenic activity by thrombin generation assay, prekallikrein activator assay, and size-exclusion chromatography. Transfusion 2014; 54: 376–83.

8. Human albumin (ÔÑ 3.3.2.006.15). State Pharmacopoeia of the Russian Federation, 13th ed. 2015. V. 3. P. 1234–8. Available from: http://www.femb.ru (in Russian).

9. 2.6.15. Prekallikrein activator. European Pharmacopoiea 9.0. Available from: http://online6.edqm.eu/ep900.

10. Order of the Industry and Trade Ministry of Russia from 14.06.2013 ¹ 916 «On approval of the Rules of production and quality control organization Medicines» (in Russian).

11. Validation of analytical methods (ÎÔÑ 1.1.0012.15). State Pharmacopoeia of the Russian Federation, 13th ed. 2015. V. 1. P. 222–34. Available from: http://www.femb.ru (in Russian).

12. Statistical analysis of the results of chemical experiment (ÎÔÑ 1.1.0013.15). State Pharmacopoeia of the Russian Federation, 13th ed. 2015. V. 1. P. 235–64. Available from: http://www.femb.ru (in Russian).

13. Human albumin solution. European Pharmacopoiea 9.0. Available from: http://online6.edqm.eu/ep900.