Polycyclic aromatic hydrocarbons (PAHs) have a wide range of carcinogenic, teratogenic, and mutagenic effects. PAHs in pharmaceutical rubber stoppers may originate from carbon black, the main raw material essential for molding, and if the residual PAHs migrate into the pharmaceutical solution, they will have an adverse effect on the safety of drugs. In this paper, it is comprehensively investigated the literature related to PAHs in pharmaceutical rubber products at home and abroad, summarized the regulatory requirements, methodological standards, and technological advances in the testing of PAHs in pharmaceutical rubber stoppers, and proposed a safety assessment strategy, with a view to provide a reference for the testing of PAHs in the compatibility study of pharmaceuticals and rubber sealing components.

OBJECTIVE To investigate the hydrolytic resistance of the inner surfaces of injection vials made of borosilicate glass in China, and explore its influence on drug quality and its influencing factors. METHODS The hydrolytic resistance of the inner surfaces of 58 batches of samples were determined. The influence on drug quality was explored through compatibility study. The influencing factors were studied by glass composition analysis and scanning electron microscope. RESULTS The hydrolytic resistance of the inner surfaces of injection vials made of middle borosilicate glass was HC1 grade and the qualified rate was 100%. The qualified rate of injection vials made of low borosilicate glass was 97.4%, including HC1 grade accounting for 38.5% and HCB grade for 58.9%. The poor hydrolytic resistance of inner surfaces would lead to increase of the pH value of drugs and glass delamination. The main factors affecting the hydrolytic resistance of inner surfaces were the high content of alkali metal oxides in glass components, the volatilization of alkali boron phase during the secondary molding process and the treatment of inner surfaces. CONCLUSION The inner surfaces of the injection bottles made of middle borosilicate glass in China have good hydrolytic resistance. However, the hydrolytic resistance of injection bottles made of low borosilicate glass in China is uneven. The samples with poor performance are at risk of incompatibility with drugs. It is suggested that enterprises optimize product formula and improve secondary molding process parameters to improve product quality.

OBJECTIVE To establish a set of accurate, reliable and easy to operate sealing inspection method for packaging systems of negative pressure lyophilized preparations. METHODS According to the packaging system internal negative pressure characteristics and seal integrity requirements, in accordance with <the Study Requirements of Technical Guide for Research on the Integrity of Packaging Systems for Chemical Injections (Trial)> and USP 1207, a new deterministic method for evaluating sealing integrity by monitoring pressure changes in packaging was developed. RESULTS Methodology validation was carried out, the standard leaky simulated positive samples of 1.1, 1.6, 4.7 and 9.9 μm were used for verification, and the accuracy was verified by mathematical model. CONCLUSION The new method is based on the packaging characteristics of vacuum lyophilized preparations, which is accurate, reliable and has higher sensitivity than the conventional methods. It can be applied to the monitoring of packaging tightness in the daily production process of drug manufacturers to ensure the quality of drugs.

OBJECTIVE To establish an HPLC method for simultaneous determination of eight antioxidants from pharmaceutical halogenated butyl rubber stoppers and their migration in freeze-dried rabies vaccines for human use, to provide reference for the research and quality control standards of rubber packaging materials and ensure drug safety. METHODS The analysis was carried out on Waters XBridge C₁₈ column (4.6 mm×250 mm, 5 μm), using mobile phase consisting of 0.1% formic acid solution (A)-0.1%formic acid methanol solution (B) eluted by a gradient program (0.0-10.0 min, 30%A→20%A; 10.0-17.0 min, 20%A; 17.0-19.0 min, 20%→1%A;19.0-37.5 min, 1%A;37.5-39.0 min, 1%→30%A;39.0-42.0 min, 30%A) at a flow rate of 1.2 mL·min^-1 at 30 ℃, the detection wavelength was set at 277 nm. RESULTS The linear relationships of the eight antioxidants were good in the concentration range of 10-500 μg·mL^-1 (R>0.999 8). The relative standard deviation of precision was 0.2%-2.4%, the relative standard deviation of stability was 1.3%-3.7%, the recovery rates of extraction were 85.7%-98.1%, and the recovery rates of migration were 97.7%-99.8%. Among the eight batches of samples from six companies, two antioxidants were detected in some pharmaceutical halogenated butyl rubber stopper samples, while no antioxidant was found in migration. CONCLUSION The method is sensitive, rapid, and accurate, which can be used to determine the extractable amounts of eight antioxidants in halogenated butyl rubber stoppers and their migration in freeze-dried rabies vaccines for human use.

OBJECTIVE To develop a quantitative analytical method for simultaneous determination of 10 photoinitiators in medicinal compound ointment tubes. METHODS Ultrasound was used to ultrasonicate the shredded medicinal compound ointment tube for 30 min, and the samples were detected by GC-MS technology. Chromatographic column was DB17-MS capillary column (0.25 mm×30 m,0.25 μm), injection port: 300 ℃, flow rate: 1 mL·min^-1, column temperature: initial 70 ℃, hold for 0.5 min, and then rise at 10 ℃·min^-1 to 300 ℃, keeping for 7 min. Injection type: liquid injection, injection volume: 1 μL. Ion source: EI, temperature: 290 ℃, voltage: 70 eV, solvent delay 5 min. RESULTS The 10 kinds of photoinitiators were well separated, with good linear relationship in the concentration range of 0.05-10 μg·mL^-1. The correlation coefficient r² was between 0.994 5-0.998 8; the average recoveries (n=9) were 84.9%-94.6%, and the RSDs were between 3.9% and 8.5%. The limits of detection were between 0.2 and 0.5 μg·mL^-1, and the limits of quantification were between 0.5 and 1.0 μg·mL^-1. CONCLUSION This method is validated to have good method accuracy and reproducibility, is easy to operate, and can be used for the determination of 10 photoinitiators in compound ointment tubes.