Method for determination of elemental impurities in metronidazole benzoate using inductively coupled plasma mass spectrometry.

The elemental impurities in pharmaceutical products have aroused widespread concern among respective supervising authorities and official pharmacopoeias since they are harmful and have no therapeutic effects. Metronidazole benzoate is used extensively to treat a variety of infections. However, impurities will inevitably be introduced in the manufacturing process of metronidazole benzoate. Hence, in this study, a sensitive method was developed for trace determination of elemental impurities in metronidazole benzoate active pharmaceutical ingredients by using inductively coupled plasma mass spectrometry in kinetic energy discrimination mode. The method was validated for system suitability, specificity, linearity, sensitivity, accuracy, and precision according to USP chapter <233> Elemental Impurities-Procedure. The method had good linearity with correlation coefficients > 0.99. The limits of detection were in the range of 0.0003-0.1411 µg/g, which was lower than the acceptable limit and indicated the high sensitivity of the method. The method was accurate with the recoveries in the range of 92%-107%. Moreover, the content of seven elemental impurities in the three batches of metronidazole benzoate active pharmaceutical ingredients by this method was originally below their limits and less than 30% of permitted daily exposure, meeting the requirement of International Council for Harmonization Q3D guidelines. Thus, this newly developed and validated method for estimating elemental impurities in metronidazole benzoate active pharmaceutical ingredients was within the permitted limit and suitable for routine use.

Aspergillus niger Fermentation Broth Promotes Maize Germination and Alleviates Low Phosphorus Stress.

Aspergillus niger is a type of soil fungus with the ability to dissolve insoluble phosphate and secrete organic metabolites such as citric acid. However, whether cell-free Aspergillus niger fermentation broth (AFB) promotes maize growth and alleviates low-phosphorus stress has not been reported. In this study, we explored their relationship through a hydroponics system. The results indicated that either too low or too high concentrations of AFB may inhibit seed germination potential and germination rate. Under low phosphorus conditions, all physiological indexes (biomass, soluble sugar content, root length, etc.) increased after AFB was applied. A qRT-PCR analysis revealed that the expression of the EXPB4 and KRP1 genes, which are involved in root development, was upregulated, while the expression of the CAT2 and SOD9 genes, which are keys to the synthesis of antioxidant enzymes, was downregulated. The expression of LOX3, a key gene in lipid peroxidation, was down-regulated, consistent with changes in the corresponding enzyme activity. These results indicate that the application of AFB may alleviate the oxidative stress in maize seedlings, reduce the oxidative damage caused by low P stress, and enhance the resistance to low P stress in maize seedlings. In addition, it reveals the potential of A. niger to promote growth and provides new avenues for research on beneficial plant-fungal interactions.