To establish an HPLC method for determination of the impurity profile in furosemide and its injection. At the same time，applying this method to detect and analyze products from many domestic and foreign enterprises，to evaluate the status quo of impurity control in API and injection，and the correlation of major degraded impurities in injection with prescription and packaging materials.

A YMC Hydrosphere C₁₈ column（250 mm×4.6 mm，3 μm）was used，and the mobile phase was 0.05% TFA solution (pH 2.23)-methanol-acetonitrile at the flow rate of 1.0 mL·min^-1，gradient elution. Detection wavelength was set at 238 nm and 277 nm and column temperature was 30 ℃. Impurity reference was used for localization and the relative retention time of each impurity was calculated. The known impurities were calculated using the principal component self-control method with correction factor，the unknown impurities were determined by principal component without correction factor.

The method for the determination of 11 kinds of known impurities，the potential genotoxic impurity in furosemide，its injection was established，the separation degree of all impurities met the requirements，and the sources of the impurities were identified by forced degradation test. The detected quantity of degraded impurity C and degraded impurity G in the injections produced by 2 to 3 companies exceeded the identification limit in ICH by 0.2%，the amount of potential genotoxic impurity furfural detected in the injection of 5 enterprises was much higher than that of the reference preparation，other impurities were the same as the reference preparation.

The established HPLC method can be used for rapid detection and analysis of impurities in furosemide and its injection. The impurity control level of injection produced by only 2 domestic enterprises is basically consistent with the reference preparation，others need to optimize prescription and packaging materials. This study can provide reference for improving the safety of furosemide injection and evaluating the quality consistency of generic drugs.

To analyze the difference of chemical constituents in rhizomes and leaves of Polygonatum sibiricum from Shaanxi Province.

Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Orbitrap HRMS) was developed to determine the chemical constituents in rhizomes and leaves of Polygonatum sibiricum from Shaanxi Province. The data were analyzed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). The structures of chemical markers in rhizomes and leaves of Polygonatum sibiricum were identified based on accurate primary mass spectrometry and secondary mass spectrometry fragment ion，combined with the reference map，software database searching and related literature.

A total of 45 compounds were identified，there were 26 chemical ingredients with significant differences distinguished by the method of OPLS-DA，including 10 amino acids，6 flavonoids，3 organic acids，2 saccharides，1coumarin and 4 alkaloids.

The chemical markers of amino acids，organic acids and alkaloids are mainly distributed in rhizomes，and the chemical markers of flavonoids are mainly concentrated in leaves part of the plant. It is suggested that the potential multiple utilization of rhizomes and leaves of Polygonatum sibiricum from Shaanxi Province.

To systematically characterize and simultaneous determine 13 chemical components (neochlorogenic acid，chlorogenic acid，cryptochlorogenic acid，luteolin-7-glucuronide，cynaroside，isochlorogenic acid B，isochlorogenic acid A，apigenin-7-glucuronide，isochlorogenic acid C，deoxyelephantopin，isodeoxyelephantopin，isoscabertopin and scabertopin) in Elephantopi Herba based on ultra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q TOF MS/MS).

UPLC-Q TOF MS/MS technology combined with sequential window acquisition of all theoretical mass spectra (SWATH) mode was used to collect data of different batches of Elephantopi Herba samples. The separation was performed on a Waters HSS T3 C₁₈(100 mm×2.1 mm，1.8 μm) column with mobile phase consisting of acetonitrile and 0.1% formic acid water solution. The flow rate of gradient elution was 0.4 mL·min^-1，the column temperature was 35 ℃ and the injection volume was 2 μL. The electrospray ionization (ESI) source was employed to collect data under both positive and negative ion modes. With reference to reference substances and relevant literatures，chemical components in Elephantopi Herba were identified. At the same time，the determination method for 13 chemical components in Elephantopi Herba was established and validated.

In this study，the cleavage patterns of different classes of compounds were summarized，and 36 chemical components were initially identified，including 20 organic acids，7 flavonoids，6 sesquiterpene lactones，1 coumarin and 2 other components. All of the analytes showed good linearity (r≥0.999 0) in the tested ranges. The precision，repeatability and stability of the method were good for the 13 components. The average recoveries were in the range of 94.9%-103.5% with relative standard deviations (RSDs) ≤3.8%. The chemical compositions of different batches of Elephantopi Herba were basically similar，but there were certain differences in the contents of 13 components.

In this study，comprehensive characterization of the chemical constituents and relative quantitative analysis of Elephantopi Herba are carried out，and a rapid and efficient qualitative analysis method of Elephantopi Herba is established by UPLC-Q TOF MS/MS，which provides a reference for the screening and rational exploitation of the medicinal substances of Elephantopi Herba，and methodological reference and data support for the quality control and development of Elephantopi Herba.

To evaluate the application of metagenomic sequencing in identification and tracking of drug-contaminating bacteria.

Both metagenomic sequencing and isolation culturing method were employed to identify and genotype bacteria in two batches of possibly contaminated gel medicines as well as the environmental samples from testing laboratory. Bacteria isolated by culturing method were identified through Gram’s stain，biochemical reaction，MALIDI-TOF-MS，16srDNA sequencing and Bacillus specific PCR. The detected Bacillus cereus were typed by multilocus sequence typing (MLST) .The metagenomic sequencing results were analyzed at the strain level using MetaPhlan software.

Both MLST and MetaPhlan analysis revealed a substantial contamination of Bacillus cereus in gel medicines as well as environmental samples，with the presence of the same Bacillus cereus group. Both metagenomic sequencing and culturing methods detected Paenibacillus，Brevibacillus and Neobacillus in gel medicines，but amplicon sequencing also detected these bacteria in environment which might be the source of contamination.

These findings indicate that metagenomic sequencing technology is reliable and has the advantage over isolation culturing in comprehensively detecting potentially hazardous bacterial species and accurately performing strain-level traceability analysis. It holds significant application value in pharmaceutical contamination identification and traceability.

To establish a new HPLC method for the determination of the related substances in tranexamic acid injection by screening new type of HPLC columns，which can avoid the use of ion pair reagents in current methods and reduce salt concentration.

The method was carried out using a Thermo Mixed-mode WCX column (150 mm×4.6 mm，5 μm)，the mobile phase consisted of 10 mmol·L^-1 sodium dihydrogen phosphate solution (adjust the pH value to 5.2±0.05 with sodium hydroxide solution)-water-acetonitrile （50:5:45），the flow rate was 1.0 mL·min^-1，the column temperature was 25 ℃，the detection wavelength was 210 nm and the injection volume was 20 μL.

The chromatographic peaks of tranexamic acid and its four impurities B，C，D and E were all separated. Good linear relationship was shown between the concentration of all the five compounds and their corresponding peak areas (r≥0.999). The LODs were 0.34，0.50，0.005 6，0.002 1，0.12 μg·mL^-1. The average recoveries (n=9) were 97.4%，100.5%，98.4% and 96.6% with RSDs of 3.9%，0.24%，0.52% and 1.4%，respectively. The test solution and standard solution were all stable within 22 h. The detection results of 5 batches of tranexamic acid injection showed that the number of unspecified impurities and the total impurities content by using the new method were better than the current ChP method.

The established method is specified and sensitive. Good separation can be achieved with low concentration of phosphate. Its applicable to the determination of related substances in tranexamic acid injection.

To establish a method for determination genotoxic impurity furfural in furosemide and its tablets. To analyze and evaluate the measurement results to provide a reference for national drug supervision and ensure drug safety.

The chromatographic column was filled with octadecylsilane bonded silica gel，and the gradient elution was performed with phosphoric acid solution and acetonitrile as the mobile phase. The detection wavelength was 276 nm. The method was validated and used to determine the furfural content in 6 batches of furosemide and 148 batches of furosemide tablets.

The detection limit of furfural was 4 ng·mL^-1 and the quantitation limit was 12 ng·mL^-1. The linearity between 0.012 0-0.602 3 μg·mL^-1 (r=1.000) was good. The average recoveries of furosemide and its tablets were 99.4% (RSD=0.99%) and 101.4% (RSD=1.3%). Furfural was detected in all batches of raw materials and tablet samples. The furfural content in the tablet products，which used the raw materials from company I，was significantly higher than that of the products obtained from company H.

This method has strong specificity，high sensitivity and good accuracy. It can be used for the determination of genotoxic impurity furfural in furosemide and its tablets. By analyzing the measurement results and discussing the sources and control strategies of furfural，quality control of furosemide tablets can be achieved.

To establish methods of thin-layer chromatography(TLC) qualitative identification and quantitative analysis of multi-components by single-marker (QAMS) according to the characterization results of the main components of Iris tectorum Maxim..

Firstly，the main components of Iris tectorum were characterized by ultra performance liquid chromatography tandem time-of-flight mass spectrometry(UPLC-Q TOF MS/MS) technology，using an ACQUITY UPLC^® BEH C₁₈ column (100 mm×2.1 mm，1.7 μm) with gradient elution using 0.1% formic acid-water (A)-acetonitrile (B) as mobile phase，and the data were collected in positive ion mode. In addition，the qualitative identification method was established by the TLC. Finally，quantitative analysis was performed on an Agilent 5 TC-C₁₈ column (250 mm×4.6 mm，5 μm). The mobile phase was 0.05% phosphoric acid water(A)-acetonitrile(B) with gradient elution. The QAMS method was established by using tectorigenin as an internal standard to establish its relative correction factor with tectoridin and irigenin，and the contents of three isoflavones were calculated by the correction factor. At the same time，the accuracy and feasibility of the QAMS method was verified by the external standard method(ESM).

Five isoflavones were characterized (tectoridin，iristectorin B，tectorigenin，irigenin and iristectorigenin A) by UPLC-Q TOF MS/MS. A TLC identification method for four components，tectoridin，iristectorin B，tectorigenin and irigenin was established. In this study，the linearity of the three components of tectoridin，tectorigenin and irigenin were good in a certain concentration range (r>0.999)，with the average recoveries of 97.7%-100.8% and the RSDs of 1.1%-2.9%，and the relative correction factors of tectoridin and irigenin were 1.114 5 and 0.827 0，respectively. And the repeatability of the correction factors was good under different experimental conditions (RSD<5%). There was no significant difference between the contents of the three analytes in ten different batches of Iris tectorum determined by QAMS and ESM. The contents of tectorigenin，tectoridin and irigenin in 10 batches of Iris tectorum from different habitats determined by QAMS were not significantly different from those determined by ESM.

Based on the characterized components of Iris tectorum medicinal materials，the TLC and QAMS methods with high-content and stable ingredients are established. The methods are simple and stable，which can be used for qualitative and quantitative analysis and quality evaluation of Iris tectorum.

To study the whole chain microbial load in the production of a traditional Chinese medicine pill.

A type of traditional Chinese medicine pills prescription was selected as the research object，including the medicinal materials and their purified medicinal materials，intermediates (mixed powder，waiting for inner packaging pills)，and finished products. The microbial limit test method was established according to the 2020 edition of the Chinese Pharmacopoeia（ChP），to detect and analyze the microbial loads of all samples collected throughout the entire chain from medicinal materials to finished products of the traditional Chinese medicine pills.

The microbial content of different medicinal materials varies greatly，and the varieties with higer risk factors for microbial contamination in medicinal materials were Perillae Folium，Pogostemonis Herba，and Angelicae Dahuricae Radix. The production process of Perillae Folium and Pogostemonis Herba needed to be improved and adjusted from “medicinal material to pure medicinal material”. There was a positive correlation between the microbial load of medicinal materials and intermediate and finished products.

The study on the microbial load throughout the entire production chain of traditional Chinese patent medicines can help us to understand the transmission of microorganisms at each stage. This knowledge is crucial for identifying weak links in the production process and the key areas for process control, and has an important guiding significance for traditional Chinese patent medicines manufacturers to improve and explore their production process.

To analyze the peptide components of bran-fried Bombyx batryticatus decoction and virtually screen anti-epileptic peptides with GAT-1 binding activity.

The peptide compounds in bran-fried Bombyx batryticatus decoction were extensively identified by micro-flow liquid chromatography-tandem mass spectrometry（μLC-MS/MS） technology. Potential anti-epileptic peptides were screened through bioinformatics and in silico simulations，including bioactivity prediction，blood-brain barrier permeability prediction，toxicity prediction，and molecular docking. Finally，molecular dynamics simulations were employed to analyze the interactions between peptides and the target protein.

A total of 384 peptides were identified from bran-fried Bombyx batryticatus decoction，and 19 peptides with higher binding affinities to GAT-1 than that of the control drug were screened as potential anti-epileptic peptides. The FDHFDFDAF exhibited the highest binding affinity，followed by the EHYAWGIK. Two peptides primarily interacted with GAT-1 through hydrogen bonds，hydrophobic，and electrostatic interactions. Molecular dynamics simulations confirmed the binding stability of FDHFDFDAF and EHYAWGIK to GAT-1.

Peptidomics and in silico virtual screening techniques facilitate the rapid discovery of active peptide components in animal-derived traditional Chinese medicine. This study has significant reference value for researching anti-epileptic peptides in bran-fried Bombyx batryticatus decoction，and provides new insights for the study of peptide components in animal-derived traditional Chinese medicine.