The article discusses the need to develop methods for determining carbon disulfide – an unacceptable impurity in infusion drugs. The relevance of this study stems from the fact that, according to the toxicology characteristic, carbon disulfide exhibits carcinogenic, teratogenic and genotoxic properties. Thus, it is one of the most dangerous toxicants for the macroorganism released by rubber plugs produced with the use of tetramethylthiuram disulfide. It is known that to date, the use of tetramethylthiuram disulfide continues in the production of rubber for stoppers used in vials of infusion medicines, which makes it necessary to consider carbon disulfide as an unacceptable admixture in infusion drugs at the level of regulatory documentation. The aim of the research. To prove that the developed method of quantitative determination of carbon disulfide in infusion preparations allows obtaining reliable results. Materials and methods. As an object of the research, infusion medicines, sealed with rubber stoppers, were chosen. As a standard sample for analysis, carbon disulphide was used. Quantitative determination of carbon disulfide in the obtained samples was conducted by gas chromatography-mass spectrometry, using a column quartz capillary size of 30 m × 0,32 mm and stationary phase of 5% diphenyl-95% -dimetilpolisiloksan (Elite-5, f-we PerkinElmer, USA). Calculation of the content of carbon disulfide was carried out using an internal standard, which was methylethylsulfide. Results. The method consists in selecting an equilibrium vapor phase from these model samples placed under stress conditions (elevated temperature, UV irradiation and oxidation) and further chromatography-mass spectrometric determination of carbon disulfide in the sample taken. The results of the determination were considered reliable if the following criteria for the suitability of the chromatographic system were fulfilled: the number of theoretically perfect plate calculated for the carbon disulphide peak was at least 40,000 theoretically perfect plate; the separation coefficient of the carbon disulfide and internal standard peaks was at least 3.5; the relative standard deviation of the values of the ratio of the areas of the carbon disulfide peaks to the areas of the internal standard peaks (RSD) was no more than 6.17%; the correlation coefficient of the linear dependence of the values of the ratio of the areas of the carbon disulfide peaks to the areas of the peaks of the internal standard on the concentration of carbon disulfide in the calibration sample was no less than 0.9978. Based on preliminary studies, the range of quantitative determination of carbon disulfide in infusion preparations is set in the range from 0 to 1000 μg/l. The conclusion. Thus, mass spectrometry is an extremely promising method of pharmaceutical analysis and allows obtaining reliable results in the range from 0.1 μg to 1 μg of carbon disulphide in 10 ml of a sample.
The article discusses the need to develop methods for determining carbon disulfide – an unacceptable impurity in infusion drugs. The relevance of this study stems from the fact that, according to the toxicology characteristic, carbon disulfide exhibits carcinogenic, teratogenic and genotoxic properties. Thus, it is one of the most dangerous toxicants for the macroorganism released by rubber plugs produced with the use of tetramethylthiuram disulfide. It is known that to date, the use of tetramethylthiuram disulfide continues in the production of rubber for stoppers used in vials of infusion medicines, which makes it necessary to consider carbon disulfide as an unacceptable admixture in infusion drugs at the level of regulatory documentation. The aim of the research. To prove that the developed method of quantitative determination of carbon disulfide in infusion preparations allows obtaining reliable results. Materials and methods. As an object of the research, infusion medicines, sealed with rubber stoppers, were chosen. As a standard sample for analysis, carbon disulphide was used. Quantitative determination of carbon disulfide in the obtained samples was conducted by gas chromatography-mass spectrometry, using a column quartz capillary size of 30 m × 0,32 mm and stationary phase of 5% diphenyl-95% -dimetilpolisiloksan (Elite-5, f-we PerkinElmer, USA). Calculation of the content of carbon disulfide was carried out using an internal standard, which was methylethylsulfide. Results. The method consists in selecting an equilibrium vapor phase from these model samples placed under stress conditions (elevated temperature, UV irradiation and oxidation) and further chromatography-mass spectrometric determination of carbon disulfide in the sample taken. The results of the determination were considered reliable if the following criteria for the suitability of the chromatographic system were fulfilled: the number of theoretically perfect plate calculated for the carbon disulphide peak was at least 40,000 theoretically perfect plate; the separation coefficient of the carbon disulfide and internal standard peaks was at least 3.5; the relative standard deviation of the values of the ratio of the areas of the carbon disulfide peaks to the areas of the internal standard peaks (RSD) was no more than 6.17%; the correlation coefficient of the linear dependence of the values of the ratio of the areas of the carbon disulfide peaks to the areas of the peaks of the internal standard on the concentration of carbon disulfide in the calibration sample was no less than 0.9978. Based on preliminary studies, the range of quantitative determination of carbon disulfide in infusion preparations is set in the range from 0 to 1000 μg/l. The conclusion. Thus, mass spectrometry is an extremely promising method of pharmaceutical analysis and allows obtaining reliable results in the range from 0.1 μg to 1 μg of carbon disulphide in 10 ml of a sample.