Validation of the method for the quantitative determination of lapatinib in tablets during the "Dissolution" test


Ya. A. Poskedova(1), Z. S. Shprakh(1, 2), E. V. Ignatieva(2), G.V. Ramenskaya(1)
1-Sechenov First Moscow State Medical University (Sechenov University), 8/2, Trubetskaya str., Mosсow, 119991, Russian Federation;
2-FSBI " N.N. Blokhin National Medical Research Center of Oncology", 24, Kashirskoe highway, Moscow, 115522, Russian Federation

Introduction. Lapatinib is used for targeted therapy of breast cancer caused by overexpression or activation of tyrosine kinase receptors of epidermal growth factor (Human epidermal growth factor receptors, HER/ErbB). For the determination of lapatinib in tablets, chromatographic methods are mainly used. However, spectrophotometry in the visible and ultraviolet regions of the spectrum can be considered as a more accessible and simple method of quantitative determination. To prove the suitability of the method for quantitative determination of lapatinib in tablets by UV spectrophotometry in the dissolution test, it is necessary to validate it. The objective of the study was to validate the method for the quantitative determination of lapatinib during the dissolution test. Material and methods. As an investigational drug, lapatinib tablets (film-coated tablets, 250 mg) obtained in the laboratory for the development of dosage forms of the FSBI " N.N. Blokhin National Medical Research Center of Oncology" was chosen. The "Dissolution" test was carried out in accordance with GPM. "Dissolution for solid dosage forms", the quantitative determination of the released substance was carried out by UV spectrophotometry, the statistical processing of the results was carried out in accordance with GPM.1.1.0013.15 "Statistical processing of the results of a chemical experiment" and the recommendations of the Guidelines for pharmaceutical industry enterprises. Results. When determining specificity, placebo interference was found to be less than 0,1%. A linear relationship between the concentration of lapatinib and the optical density of the solution has been proven. The values taken as true lay within the confidence intervals of the corresponding average results of analyzes obtained experimentally using validated method. When determining the repeatability, the value of the relative standard deviation (RSD, %) for the degree of dissolution of lapatinib did not exceed 2%. For the validated method, acceptable specificity, linearity, accuracy, and precision were proven in the concentration range from 0.025 mg/ml to 0.061 mg/ml, which corresponds to the range from 55% to 135%. Conclusion. Validation of the method for lapatinib quantitative determination during the “Dissolution” test for the dosage form of film-coated tablets, 250 mg has shown the possibility of its use for quality control of the medicinal product.

dissolution test
UV spectrophotometry
generic drug.

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