ABSTRACT
Objective: According to the ICH guideline, the long-term stability and accelerated stability testing for Er-Zhi-Wan (water honey pills) has been carried out on the basis of the qualitative and quantitative analysis on multiple components in Er-Zhi-Wan by using UPLC-Q-TOF/MS method. In addition, the influence factors of the preparation (packing material and sealing process) were investigated by UPLC method. Methods: The analysis was performed on an Acquity UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with the mixture of acetonitrile-water-formic acid as mobile phase, the flow rate was 0.2 mL/min and MS scanning mode was positive and negative. According to the ICH guideline, the 18 months long-term stability [(25 ± 2) ℃, relative humidity (RH) of (60 ± 5)%], accelerated stability testing [(40 ± 2) ℃, RH of (75 ± 5)%], and influence factors of preparation (packing material and sealing process) for Er-Zhi-Wan (water honey pills) have been carried out by the UPLC method. Results: A total of 20 chemical compounds (salidroside, wedelolactone, 10-hydroxyoleoside dimethyl ester, oleoside-11 methyl ester, loganic acid, echinacoside, nuezhengslaside, oleuropein acid, verbascoside/isoverbascoside, nuezhenoside, specnuezhenide, ligustroflavone, isomer of specnuezhenide, safghanoside F, isonuezhenide, nuezhenidic acid, oleuropein, nuezhenoside-G13, oleonuezhenide, and 3-O-cis-p-coumaroyltormentic acid) were identified in the qualitative study. The content of these compounds was measured by the established quantitative and semi-quantitative research methods. In long-term stability testing, the 20 compounds were all remained stable. However, in the accelerated testing, the content of 11 chemical compounds (10-hydroxyoleoside dimethyl eser, echinacoside, nuezhengslaside, oleuropein acid, verbascoside, nuezhenide, specnuezhenide, ligustroflavone, nuezhenidic acid, nuezhenoside-G13, and oleonuezhenide) decreased obviously. Taking soda-lime glass as the packaging material, the stability of Er-Zhi-Wan (water honey pills) was improved than the commercial package under the same sealing conditions. The airtightness of the packaging materials played a significant part on the pill's stability under different sealing conditions. Conclusion: The study offers the scientific and technical support for the quality control and the clinical safety of the preparation in Chinese materia medica.