Objective  To establish a simulation system to investigate the change trend of benzene produced by the decarboxylation reaction of sodium benzoate, adopt the control variable method to find out the best conditions of the reaction, and further explore the influence of light and temperature on the decarboxylation reaction.

Methods  Using headspace gas chromatography–mass spectrometry (HS-GC-MS) technology, the chromatographic column was Agilent DB-624 capillary column (30 m×0.32 mm, 1.8 μm), the injection port temperature was 200 ℃, and the detector temperature was 250 ℃. The carrier gas was nitrogen, the volume flow rate was 2.0 mL/min, and the split ratio was 10 ∶ 1. The program heating conditions were as follows: the initial temperature was maintained at 40 ℃ for 6 minutes, and then the temperature was raised to 230 ℃ at a rate of 30 ℃/min and maintained for 10 minutes. Using headspace injection method, the headspace bottle temperature was 90 ℃, and the equilibrium time was 30 minutes. Using selective ion scanning mode, qualitative and quantitative analyses were conducted on characteristic ions m/z 78, 77, and 51.

Results  Under the coexistence of 0.3 g sodium benzoate, 10  mmol/L ascorbic acid, and 1 mmol/L transition metal ion Cu^2⁺, the reaction of sodium benzoate decarboxylation to generate benzene was most significant, and the amount of benzene generated sharply increases with the decrease of solution pH. There was a significant interaction among various influencing factors. Light exposure and heating at 40 ℃ had little effect on the decarboxylation reaction, while under the high temperature condition of 60 ℃, the increase in benzene content in most samples significantly exceeded the limit requirements specified in the pharmacopoeia.

Conclusion  Through the study of influencing factors and destructive experiments, the key conditions for the conversion of sodium benzoate to benzene have been clarified, providing data support for the risk assessment of benzene contamination in marketed drugs, and also providing strong technical basis for pharmaceutical companies to formulate prescription processes.

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