On the assessment of contamination and analysis of control samples in toxicokinetics studies

Relevance. The evaluation of control samples contamination is a necessary element for confirming the correctness of toxicokinetic studies (TK), concomitant with the study of toxicity of drugs and products. At the same time, insufficient elaboration of existing regulatory documents necessitates discussion of practical aspects and improvement of the regulatory framework. Purpose. The work is devoted to the consideration of experimental experience of control samples contamination in TK studies. Materials and methods . As experimental examples, two studies of TK drugs performed using rabbits with oral administration of study drugs for 28 (Study 1) or 90 (Study 2) days were considered. Results . Study 1 revealed a contamination level of 17–25 % (on the first and last days of study drug administration, respectively). Contamination of bioassays can occur in vivo (contamination of animals) and ex vivo (at the stage of bioassay sampling, at the pre-analytical stage and analytical stage). The nature of the analyte detection in the samples made it possible to exclude contamination in vivo , and the results of an internal investigation suggested that it occurred at the stage of biosample selection. In Study 2, a number of preventive measures were implemented and a slight level of contamination was obtained (0.83 %), which did not affect the completeness and correctness of results interpretation. Conclusion . Based on experimental experience, recommendations for minimizing and preventing contamination of control samples during the biological part, pre-analytical and analytical stages of studies were formulated. Presumably, in the presence of a random nature of contamination indicating its ex vivo origin, the level of contamination not exceeding 25 % can be considered insignificant, i.e. not leading to further deviation and cancellation of the results of the entire study