Currently, a comprehensive approach is being developed for the integrity control of fuel rod claddings in pressurized water reactor (PWR) nuclear power plants. One of the key stages is the reliable detection of leaking fuel rods within the reactor's active zone during power operation. This study examines the general trends in the activity of fission product radionuclides in the primary coolant of various generations and designs of PWRs. The experience of Novovoronezh Nuclear Power Plant is considered regarding the method of sampling and separation of inert radioactive gases from the primary coolant. A comparison is made between different methods of measuring inert radioactive gases in the primary coolant: direct spectrometry, cryogenic method, and vacuum extraction method. The issue of reliable detection of fuel rod leakage during reactor operation is discussed, using the example of Unit 5 at Novovoronezh Nuclear Power Plant. Comparative results are presented for the analysis of the integrity of fuel rod claddings based on key reference radionuclides. The most reliable results indicating fuel rod leakage were obtained through the control of specific activities and analysis of changes in the ratio of inert radioactive gases using the vacuum extraction method. Control of the specific activity of inert radioactive gases in the primary coolant enables a highly reliable assessment of the condition of physical barriers. The proposed method of sampling and separation of inert radioactive gases demonstrates high reliability and convergence of results, serving as an additional tool for integrity control of fuel rod claddings during power operation. Having representative data on the specific activities of inert radioactive gases allows for a reliable assessment of the condition of fuel rod claddings within the reactor core.