Macrolide antibiotics are broad-spectrum, with activity against a range of Gram-positive, Gram-negative organisms and some anaerobes. The components of macrolide antibiotics are generally complicated. Therefore, it is very important to establish impurity profiles of these antibiotics to ensure their safety and process control. Compared with classical methods, the liquid chromatography-mass spectrometry method is particularly advantageous to characterize minor components at trace levels in terms of sensitivity, efficiency and selectivity, thus more and more widely used in establishments of impurity profiles. In this study, the general approaches to characterize minor components in complex pharmaceutical matrix, fragmentation pathways of 14- and 16-membered macrolide antibiotics and the establishment of the impurity profile of acetylspiramycin were given to provide valuable enlightenments to establish the impurity profiles of pharmaceutical products.

In recent years, more and more researchers focus on the selectivity of RP-HPLC columns. Among these columns, C18 column is the most commonly used the column. Yet even the same filler can not give us the same separation effect with the columns of different brands and different types, therefore, it is important to choose the suitable HPLC column for carrying out an experiment. After study in recent years, some column classification, selection methods (e.g.: column parameter method, F value method) have been achieved and contributed to the finding of suitable columns and reducing the blindness of column selection. This paper summarizes the advantages of these methods and their limitations in the application process, and gives some advices and expectations to pharmaceutical analysis works based on the works of other researchers.

Objective To study the strain difference in response to the antidepressant fluoxetine in mouse tail suspension test.Methods Two outbred mouse strains (KM and ICR) and three inbred mouse strains (C57BL/6,Balb/c and DBA/2) were used in this study.They were treated with the selective serotonin reuptake inhibitor (SSRI) fluoxetine or saline and the immobility time in tail suspension test was recorded.Results There was significant difference of baseline immobility time among different stains with C57BL/6 the most immobile((145.0 ±16.8) s) and DBA/2 the least ((34.5 ± 6.1)s).Fluoxetine significantly decreased the immobility time in C57BL/6 ((116.0 ± 10.3) s vs (145.0 ± 16.8) s) of control),Balb/c ((44.3 ± 6.2) s vs (75.3 ± 10.3) s) of control) and DBA/2 mice ((16.6 ± 4.3) s vs (34.5 ± 6.1) s) of control),while the immobile time of KM and ICR mice was not influenced by fluoxetine.Conclusion The effects of fluoxetine in tail suspension test are strain dependent.Fluoxetiue exhibits antidepressant effects in C57BL/6,Balb/c and DBA/2 mice,but not in KM and ICR mice.

A near infrared (NIR) method for the detection of illegal addition of sildenafil citrate in capsules of Chinese traditional medicine was constructed. The diffuse reflectance near infrared spectra were recorded using integrated sphere and fiber optics respectively. Using the spectra of the sildenafil citrate standard as Reference spectra, the threshold of the correlation coefficient was set up based on the minimum effective concentration of the sildenafil citrate. By comparing the threshold with the correlation coefficient between the tested spectra and the Reference spectra in the selected spectral range, the tested sample contains sildenafil citrate is determined. For the integrated sphere method, the spectral range of 6070-5800 cm~(-1) and 4170-4070 cm~(-1) were selected, and 70% was set as threshold. For the fiber method, 6070-5800 cm~(-1) and 65% were used. 79 and 247 batches of the Chinese traditional medicines contained sildenafil citrate collected from the Chinese market were used to validate the two methods separately. The accuracy of the integrated sphere method was 91.14%, and that of f iber method was 87.45%.

With the establishment of HPLC and LC-MS methods to determine the related substances and the content of active pharmaceutical ingredient (API) in ipratropium bromide aerosol products, several packing material-related impurities were identified, including antioxygen BHT and antioxygen 2246. Results showed that these leachable additives from the packing materials may present at a relative high level in the drug solution, and the low content of API in the drug products is usually due to the adsorption of the packing material as well as the leaking of contents. The current available assay methods for the control of ipratropium bromide aerosol products are often lack of specificity and unable to assure the drug quality effectively. To meet the increasing attention on the regulations of drug packing materials, our research would be a pilot study, indicating that the inappropriate packing materials could cause the migration and adsorption of the active ingredients, and the importance to have compatibility studies between packing materials and drugs.

The near infrared ( NIR ) spectra of 76 batches of the amoxicillin capsules from different manufacturers and their corresponding content powder without capsules cell were used to find some quantitative indicators to evaluate whether the piecewise direct standardization ( PDS ) algorithm succeeded in NIR quantitative model updating. 54 batches were used to construct the NIR quantitative model for capsule preparation. All the NIR spectra of amoxicillin capsules were divided into five classes by cluster analysis, and each class can be regarded as a homology sample set. The average spectrum for each homology sample set was calculated. Ten to Fifteen spectra were selected from each homology sample set as the corresponding master spectra of the PDS algorithm to correct all the NIR spectra of the amoxicillin content powder respectively. Then the corrected spectra were predicted by the constructed NIR quantitative model for amoxicillin capsules. The prediction error for each corrected powder spectrum, and the correlation coefficient between each corrected powder spectrum and the average spectrum of the corresponding homolog sample set which the PDS master spectra came from, were calculated. Finally, the relationship between the prediction error and its corresponding correlation coefficient were studied. It was found that the correction results correlated closely with the selected master spectra set in PDS algorithm. The bigger the correlation coefficient ( r) , the better the correction results. In general, when r is less than 99%, it can be judged that the PDS correction is failed. At this condition, the prediction error is often more than 5%. Therefore, the correlation coefficient between the corrected spectrum and its corresponding average spectrum of the homology sample set can be used as an indicator to evaluate the efficiency of the PDS correction.

Objective To investigate the in-vitro antibacterial effect and sterility test of Danshen injection(DI). Methods Three kinds of in-vitro antibacterial and bacteriostatic methods were used to investigate the in-vitro antibacterial effect of DI and to establish its sterility test according to the results of the antibacterial effects. By validation test, the validity of its sterility test was evaluated. Results The results of doubling dilution test showed that the minimum bacteriostatic concentration of DI is 0.098 mg/mL, and its minimum bactericidal concentration is 1. 563 mg/mL in ethanolsulfate medium and 0.195 mg/mL in nutrient meat soup medium. Rate of recovered bacterium was much more than 80% by membrane filtration method. Conclusion DI has strong in-vitro bacteriostatie effects for staphylococcus aureus and the effectual method of its sterility test is membrane filtration method.

The quality of some earlier developed antibiotics is usually ensured by the combination of HPLC purity and microbiological potency measurement in the pharmacopoeias of various countries because the relationship between their purity and potency is not clearly quantified. Due to potency is assessed using certain units of measurement, it can not be directly traced to the international system of units (SI unit). This has become a hotspot in the study of the quantitative relationship between purity and potency of antibiotics. It would be quite an achievement to simultaneously determine both purity and potency using HPLC methods during quality control. This study evaluated a multicomponent antibiotic product, gentamycin, as a test sample. First, pure samples of the C components of gentamycin: C1a, C2, C2a and C1 were prepared, separately. Second, quantitative relationship (theoretical potency) between the purity and potency of each C component of gentamycin were determined using 1H NMR, HPLC-ELSD and microbiological assay method. One milligram of gentamycin C1a, C2, C2a and C1 was equal to 1 286.98, 1 095.74, 1 079.52 and 739.61 gentamycin units, respectively. Finally, a method for the determination of gentamycin potency was established based on the proportion and content of C components of gentamycin. The unification of purity and potency for gentamycin was achieved using only HPLC-ELSD. It is also demonstrated that C components of gentamycin and micronomicin produce the same responses under ELSD, which means that it is not necessary to prepare separate reference standards for each C component of gentamycin and that quantitative testing can be performed accurately using only one micronomicin reference standard. This study simplified the previous method for the determination of the content of C components of gentamycin using HPLC-ELSD. The developed method is suitable for regular use as a part of quality control and can simplify the rigmarole quality control procedures provided in current pharmacopeias.

Abstract: Construction of a successful near infrared analysis model is a complex task. It spends a lot of manpower and material resources, and is restricted by sample collection and model optimization. So it is important to study on the extended application of the existing near infrared (NIR) models. In this paper, cephradine capsules universal quantitative model was used as an example to study on the feasibility of its extended application. Slope/bias correction and piecewise direct standardization correction methods were used to make the universal model to fit to predict the intermediates in manufacturing processes of cephradine capsules, such as the content of powder blend or granules. The results showed that the corrected NIR universal quantitative model can be used for process control although the results of the model correction by slope/bias or piecewise direct standardization were not as good as that of model updating. And it also indicated that the model corrected by slope/bias is better than that by piecewise direct standardization. Model correction provided a new application for NIR universal models in process control.

Objective:To interpret the main revision of the microbiological examination for nonsterile products:tests for specified microorganisms in Chinese Pharmacopoeia (2015 edition). Methods:The microbiological examination for nonsterile products:tests for specified microorganisms in Chinese Pharmacopoeia (2015 edition) was compared with the relevant content in the 2010 edition, and then the differences were investigated. Results:Microbiological examination for nonsterile products:tests for specified microorganisms in Chinese Pharmacopoeia (2015 edition) had been revised at a comparatively large scale in the inspection items, test method, micro-bial culture system, the quality control concept and so on. Conclusion:Microbial inspection system in Chinese Pharmacopoeia (2015 edition) is gradually improved to become a high standard check system in line with the international standards.