Method Research On Determining The Organic Residual Solvents In Several Drugs

Drug safety problems have always been a hot concern of the society. So from the life perspective, it has a direct impact on the lives and safety of the people; from the perspective of national economic development, it affects the competitiveness of China’s pharmaceutical industry in the international market. Regardless of effects on either side, drug safety problems are closely bound up of the social stability. Thus, strengthening the security control of the drugs is extremely urgent. Residual solvents in pharmaceuticals are volatile organic chemicals that are used in and/or produced during the manufacture of drug substances, excipients or drug products. The residual solvents cannot be completely removed by practical manufacturing techniques. The presence of residues solvent in drugs is a potential risk of drug toxicity, which has perplexed drug manufacturers for many years. Therefore, it is a greatly significant research work to explore and optimize the detection of residual solvents in pharmaceuticals to ensure the quality and safety of medicines.This paper, based on the guidance of China pharmacopoeia and related regulations and articles regarding residual solvents, are combined with several practical drug manufactures using organic solvents. Direct injection, gas-liquid headspace injection, gas-solid injection all with gas chromatography are used to detect variety of residual solvents in drugs so as to solve existing problems, which is of great significance in practical applications. The full article is divided into four chapters. The first chapter summarized the general condition of residual solvents and related requirements of detect methods. It mainly described the residual solvents’official definition, categories, limits and official detect methods, as well as summaries of theories of the innovative methods and published researches on the organic residual solvent detection. In chapter two, a gas chromatography with direct injection was established to determine the content of the mixed solvent petroleum ether in Ibuprofen. Besides, selection studies on the columns’type, column’s temperature, flow rate and injection’s temperature were also processed. The largest peak among the mixed solvent was set as a standard in order to do the research on the methodology. The result showed that R≥0.999in the linearity, accuracy and precision of the experiment were good, and the method was easy and reliable. In chapter three, the direct injection and gas-liquid headspace injection was chose properly to determine the residual solvents in fasudil hydrochloride. The gas-liquid headspace injection was used to detect the methanol, dichloromethane and methyl tert-butyl ether in fasudil hydrochloride because of their low boiling points, which made it more environmental and simple. Referring to the dimethylform amide with high boiling points, direct injection was selected for high sensitivity. It’s due to the proper use of the two injection ways that the residual solvents’linearity in their range are good, RSD are all less than5%, and the average recoveries are in the range of89.6-110.5%. The experimental results are accurate and reliable. The chapter four is about determination of the residual organic volatile solvents in testosterone cypionate by Headspace Gas Chromatography. The research optimized the detection method of benzene. Using the solid headspace gas chromatography, the sensitivity of the benzene was improved and interference of other solvents is avoided. In addition, Headspace Gas Chromatography was discussed deeply and perfected its practical use in the determination of the organic residual solvents.