01 Introduction

Today we will share the stability study of specific impurities of the rheumatic drug - Eguratimod. Eguratimod has anti-inflammatory, immunoglobulin and cytokine production inhibition, anti-bone resorption and bone formation promoting effects.

02 Experimental plan

In this experiment, our center conducted a solution stability study on the three coded impurities of Iguratimod according to the chromatographic conditions used under the "Related Substances" inspection item in "Iguratimod" (standard number YBH02792011). The sample catalogue number and structure are shown in Figures 1 and 2:

Figure 1: impurity cargo number and structure type

Figure 2: Corresponding diagram between impurity cargo number and code

In this experiment, the experimenter took the appropriate amount of samples RM-I071835, RM-I071848 and RM-I071855, placed them in acidic, neutral and alkaline solutions, and placed them at room temperature and pressure for 0,3,6,12,24 hours before chromatographic detection. Chromatographic conditions refer to the chromatographic conditions used under the "Related Substances" inspection in Iguratimod (Standard No. YBH02792011). The solution stability of the sample was determined based on the extension of the sample solution placement time.

03 experiment conclusion

During the process of sample RM-I071855 in acidic, neutral and alkaline solutions, the relative standard deviation is less than 2.0%. It can be considered that sample RM-I071855 is relatively stable in acidic, neutral and alkaline solutions for 24 hours. The detection data of sample RM-I071855 in solution environments with different pH values are summarized as follows:

Figure 3: Summary of the RM-I071855 solution stability data

During the course of sample RM-I071835 in acidic and neutral solution, the relative standard deviation was greater than 7.0%. In contrast to the detection map placed for 0 hours, the main peak area was reduced by about 15% in the detection map after 3 hours of placement, with little change during the course from 3 hours to 24 hours, and the sample was no longer degraded. Therefore, RM-I071835 is partially degraded in acidic and neutral solutions in a short time, but not in complete degradation, and the degradation will stop after about 3 hours of sample solution preparation. However, the stability monitoring of RM-I071835 in the alkaline solution varies greatly and the impurity increases greatly. Compared to the detection map placed at 0 hours in acidic and neutral solution, the detection map of sample RM-I071835 placed in alkaline solution showed that most of the sample had been degraded, and the detection map placed at 3 hours in alkaline solution showed that the sample had been completely degraded. So the sample RM-I071835 will degrade very quickly in the alkaline solution, and it will be completely degraded. The detection data of sample RM-I071835 in solution environments with different pH values are summarized as follows:

Figure 4: Summary of RM-I071835 solution stability data

Figure 5: Solution stability data in RM-I071835

Figure 6: Solution stability data diagram at RM-I071835 under neutral conditions

Figure 7: Solution stability data under RM-I071835

The peak area of the sample RM-I071848 in acid and neutral solution, and the relative standard deviation was greater than 7.0% (7.73% in acid and 28.29% in neutral conditions). During the process of placing the sample in the alkaline solution, the main peak area quickly disappears, and the sample RM-I071848 has been completely degraded in the process of sampling with the alkaline dilution agent, so the sample RM-I071848 will degrade quickly in the alkaline solution, and it will be completely degraded. The detection data of sample RM-I071848 in solution environments with different pH values are summarized as follows:

Figure 8: Summary of the RM-I071848 solution stability data

Figure 9: Solution stability data in RM-I071848

Figure 10: Solution stability data diagram under RM-I071848 neutral conditions

Figure 11: Solution stability data diagram under RM-I071848 alkaline conditions

04 summary

In conclusion, through this experiment, we found that the sample RM-I071855 is more stable, the sample RM-I071835 and RM-I071848 in acidic and neutral solution is less stable, partial degradation, in the stability of alkaline solution, all degradation will occur in a short time. The above samples need special attention in the process of preservation and detection, it is recommended to use now, it is not suitable for reserve liquid. If the stability data of the above 3 samples is needed, you can consult our company.