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 establish an HPLC method for the simultaneous determination of eight components including salvianic acid A sodium，geniposidic acid，phellodendrine，salvianolic acid B，palmatine，berberine，atractylodin，tanshinone Ⅱ_A in Shuangshi Tonglin capsules.

The determination was performed on a Capcell Pak MG Ⅱ C₁₈ column (250 mm×4.6 mm，5 μm) with the mobile phase consisting of acetonitrile-water(containing 0.1% phosphoric acid)-water(containing 0.1% phosphoric acid and 0.2% triethylamine，pH 6.0) in a gradient mode at a flow rate of 1.0 mL·min^-1. The column temperature was set at 30 ℃，the injection volume was 10 μL，and the detection wavelength was 280 nm (0-13.4 min）for salvianic acid A sodium，238 nm (13.5-17.0 min) for geniposidic acid，280 nm （17.1-51.0 min）for phellodendrine，salvianolic acid B，345 nm（51.1.1-70.0 min）for palmatine，berberine，336 nm（70.1-78.0 min）for atractylodin and 268 nm(78.1-90.0 min)for tanshinone Ⅱ_A.

Salvianic acid A sodium，geniposidic acid，phellodendrine，salvianolic acid B，palmatine，berberine，atractylodin，tanshinoneⅡ_A had good linearities in their respective linear ranges with all linear correlation coefficients ≥ 0.999 5 and RSDs of the precision，repeatability and stability less than 2.0%. The average recoveries were 101.3%，98.2%，97.3%，98.1%，96.6%，97.9%，98.7%，99.6%，with RSDs lower than 2.0%. The contents of the above eight components in three batches of samples was 4.47-5.51 mg·g^-1，0.93-1.44 mg·g^-1，1.00-1.07 mg·g^-1，5.72-8.67 mg·g^-1，0.64-0.69 mg·g^-1，1.62-1.90 mg·g^-1，0.055-0.088 mg·g^-1，0.29-0.44 mg·g^-1，respectively.

The proposed method is rapid，sensitive and specific，which can be used for determination the contents of eitht components in Shuangshi Tonglin capsules.

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 establish the quantitative analysis of multi-components by single marker（QAMS） method to simultaneously determine the contents of rutin，hyperoside，isoquercetin and quercetin in Zanthoxyli Pericarpium and Pericarpium Zanthoxyli Armati，and compare the differences in flavonoids contents.

Methanol extract of Zanthoxyli Pericarpium was analyzed on an Agilent Eclipse Plus C₁₈ (250 mm×4.6 mm，5 μm) chromatographic column. The mobile phase was acetonitrile(A)-0.1% formic acid(B) in a gradient elution. The flow rate was 1.0 mL·min^-1. The column temperature was 35 ℃，and the detection wavelength was 360 nm. The injection volume was 10 μL. Using hyperoside as the internal standard substance，the relative correction factors for the other 3 components were calculate and the flavonoids contents in Zanthoxyli Pericarpium and Pericarpium Zanthoxyli Armati were determined.

The 4 components had good linear relationship within their respective ranges (r≥0.999 9). The average recovery rates of Zanthoxyli Pericarpium were 99.3%-105.1% (n=6)，while thoes of Pericarpium Zanthoxyli Armati were 91.9%-99.8% (n=6). The relative average deviations of content of Zanthoxyli Pericarpium were 0.05%-3.37%，and the relative average deviations of content of Pericarpium Zanthoxyli Armati were 0.02%-3.28%. The results obtained by QAMS method were close to those obtained by the external standard method(ESM).

This method of QAMS method is accurate and reliable. The total amount of flavonoids in Pericarpium Zanthoxyli Armati is significantly higher than that in Zanthoxyli Pericarpium. Which provides reference for the comprehensive evaluation of the quality research of Zanthoxyli Pericarpium and Pericarpium Zanthoxyli Armati.

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 establish a low-field and high-field nuclear magnetic resonance (NMR) technique for the determination of pyridoxine hydrochloride. To compare the differences between the results of method validation and sample content.

Using deuterated water as the solvent and maleic acid as the internal standard，method validation of quantitative nuclear magnetic resonance (qNMR) was accomplished with both 80 MHz low-field NMR and 500 MHz high-field NMR instruments. The content of pyridoxine hydrochloride was also determined.

The linearity of pyridoxine hydrochloride was good in the range of 10-30 mg·mL^-1，and the linear correlation coefficients were 0.999 8 and 0.999 6 for the low-field and high-field NMR，respectively. RSDs of the low-field and high-field NMR measurements were 1.4% and 0.040%，respectively. The contents were 100.4% and 100.8%，which were in agreement with the results from the mass balance method (100.0%). And the repeatability RSD was 0.20%. For the same concentration of the sample，the signal-to-noise ratio (S/N) of high-field NMR was about 100 times that of low-field NMR，and the half-peak width was 1/15 of that of low-field NMR.

Both low-field and high-field NMR instruments gave accurate results in the determination of pyridoxine hydrochloride content. However，low-field NMR was only suitable for compounds with simple structures. In the actual content determination，it is necessary to choose the appropriate instrument according to the structure and solubility of the sample to be tested.

To establish an integrated model of biosensing technology for the study of zebrafish，and to study and verify the interaction between cetirizine hydrochloride，fexofenadine hydrochloride，mizolastine，and ebastine，with the key target of allergic rhinitis，macrophage migration inhibitory factor（MIF）.

A MIF-high electron mobility transistor(HEMT) biosensor was constructed using AlGaAs/GaAs HEMT as the sensing element and MIF as the biological element. The interaction strength between cetirizine hydrochloride，fexofenadine hydrochloride，mizolastine，and ebastine and MIF was characterized. Furthermore，a zebrafish immune inflammation model was established. The number of neutrophil migration in the blank control group，model group，positive drug group，and low，medium，and high-dose drug groups were recorded. And the drug inflammation inhibition rate were calculated.

Cetirizine hydrochloride exhibited the strongest binding ability to MIF，with a dissociation constant of 7.05×10^-13 mol·L^-1. The K_D for the interactions between fexofenadine hydrochloride，mizolastine，and ebastine with MIF were 2.34×10^-8 mol·L^-1，1.94×10^-7 mol·L^-1 and 2.44×10^-8 mol·L^-1，respectively. All of them had binding effects with MIF. Further the validation using the zebrafish immune anti-inflammatory model revealed that all four antihistamines significantly reduced the number of neutrophil migrations，among which 100 μmol·L^-1 of cetirizine hydrochloride achieved a neutrophil migration inhibition rate of 68.5%.

This study explores the interaction between antihistamines and the key protein target of AR through the integration of biosensing technology and zebrafish experiments. It was found that MIF is a potential target for antihistamine drugs to exert their pharmacological effects. It provides an important reference for research on drug efficacy and its association with targets.

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.

To develop a novel and efficient assay for the determination of free formaldehyde content in vaccines，and to compare the results with the method of the Chinese Pharmacopoeia(ChP) 2020 edition.

Vaccine samples were added directly into headspace vials without any pretreatment and tested after mixed with a new derivatization reagent，1% p-toluenesulfonic acid-ethanol solution (1% TsOH-EtOH solution). The concentration of the reagent，the dosage and the optimal derivatization conditions (headspace incubation temperature and time) were tested and confirmed. A DB-624 gas capillary column was used with temperature programming. The detector was a hydrogen-ion flame detector (FID) and the sample was injected in headspace.

The linear range was 0.25-100 μg·mL^-1（r=0.999 5），the detection limit and the quantification limit were 0.10 μg·mL^-1 and 0.25 μg·mL^-1，respectively. The recovery rates of several kinds of vaccines were all over 94%，and the RSDs were all less than 6%，which were in line with the requirements of specificity，precision and durability. There were no significant differences between the results of multiple batches and those determined by ChP 2020 methods.

In this paper，a novel derivatization reagent (1% TsOH-EtOH solution) was developed and validated for the determination of free formaldehyde content in vaccines，which is simple，efficient and can achieve high-throughput detection. The method can just solve the problems in other current detection methods. The method of derivatization headspace gas chromatography for the determination of free formaldehyde content is applicable to vaccines and other biologics，and provide a reference for chemicals，traditional Chinese medicine and excipients.

To establish the first batch of national drug reference standard of L-methionine sulfoxide.

The molecular structure of methionine sulfoxide was confirmed by the methods of IR，NMR and high resolution MS. Moreover，the moisture，residual solvents，residual ignition and related substances of L-methionine sulfoxide were determined，and then，its hygroscopicity，homogeneity and stability were also observed. Finally，mass balance method，HPLC and quantitative NMR were applied to determine and calculate its contents.

The results of experiments showed the structure of L-methionine sulfoxide were confirmed，its contents of moisture，residual ignition，metal elements and related substances were 0.23%，0.20%，10.87 μg·g^-1 and 5.09%. The residual solvents were not detected in the samples. The final content of methionine sulfoxide was 94.5% by mass balance method. The contents of this batch of L-methionine sulfoxide were uniform，and it is stable in short-terms.

The first batch of national drug reference standard of L-methionine sulfoxide was established，and it is used for the inspection for related substances of amino acid drug，which is helpful in normalizing drug quality and guaranteeing drug safety.

To establish an HPLC method for the determination of related substances in olaparib raw materials.

By using YMC-Pack pro C₁₈ AS(150 mm×4.6 mm，3 μm) column，0.05 mol·L^-1 potassium dihydrogen phosphate (pH 3.0 adjusted with dilute phosphoric acid)-methanol-acetonitrile (90:5:5) was as mobile phase A and methanol-acetonitrile-water (45:45:10) was as mobile phase B，in gradient elution，with flow rate of 0.8 mL·min^-1. The column temperature was 30 ℃，the detection wavelength was 210 nm，and the injection volume was 10 μL.

The solvent blank did not interfere with the determination of relevant substances in the test solution，the known impurities Ⅰ-Ⅶ and unknown impurities in the system suitability solution were well separated in the chromatographic system. Olaparib had a good linear relationship with its peak area in the concentration range of 0.083-333.133 μg·mL^-1. The concentrations of impurities Ⅰ-Ⅶ were 0.05-3.0 μg·mL^-1，there were good linear relationships with their peak area，and their r were 0.999 7 or above. The average recoveries of impurities Ⅰ-Ⅶ were all above 92.0%，and RSDs were less than 4.0%.

The HPLC method for the detection of the related substances of olaparib raw materials has strong specificity，high sensitivity，high accuracy and good precision，which can meet the requirements for the detection of related substances of olaparib raw materials.

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 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 establish a method for the quantitative detection of bacterial endotoxins in human peripheral blood mononuclear cell (PBMC) suspensions and to validate the feasibility of the detection method.

According to the standards for photometric determination of bacterial endotoxin in General Notice 1143 of Chinese Pharmacopoeia (ChP) part Ⅲ (2020 edition) and 1085 of USP. A preliminary detection method of bacterial endotoxin content in PBMC suspension was established from standard curve reliability verification and primary interferential screening test. Bacterial endotoxins in three batches of PBMC suspensions were quantitatively detected by this method.

In the establishment of standard curve and reliability verification test，the linear regression equation was lgt= 2.910 9-0.300 1lgC，r=-0.999 8，negative control t>3 600 s，repeated reaction tube RSDs were less than 3%，the standard curve was established successfully. The results of the primary interferential screening test showed that the PBMC suspension had interference on limulus test at the dilution ratio of 10 and the recovery rate was close to 100% at the dilution ratio of 80，indicating that 80-fold was the best interference dilution ratio without interference. The results of the three batches of samples showed that the endotoxin contents were all less than 1.0 EU·mL^-1 at the dilution ratio of 80，and the RSDs were less than 10%. The positive recoveries were 80.8%-100.3%，which complied with ChP 2020.

This method can quickly and quantitatively detect the content of endotoxin in PBMC suspension.

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 classify the microbiological examination methods of live microecological products according to the results of suitability test for the enumeration method，and establish the decision-making method for microbiological examination of live microecological products.

The suitability test of the microbiological examination method of live microecological products was performed according to the requirements of the General Chapter 1105 in the Chinese Pharmacopoeia Vol Ⅳ. Escherichia coli，Staphylococcus aureus，Bacillus subtilis，Pseudomonas aeruginosa，Candida albicans and Aspergillus niger were used as the test strains. Tryptic Soy Agar，Sabouraud Dextrose Agar，Rose Bengal Agar and Rose Bengal Agar Ⅱ were used as medium.

For live microecological products composed of anaerobic bacteria or microorganisms with growth characteristics significantly different from the test strains，the suitability test for the method could be performed according to General Chapter 1105. For live microecological products containing Bacillus and enterococcus，the suitability test for the fungal enumeration method could be performed according to General Chapter 1105. Live microecological products could not be tested for suitability of the method due to the influence of the component microorganisms，gram-negative bacteria could be controlled using selective medium. In addition，some potentially harmful microorganisms could be controlled based on risk assessment according to the route of administration and the population of drug users.

This study provides a basis for the selection of the microbiological examination methods for live microecological products，and further complements and improves the quality standard system of live microecological products.

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 an inductively coupled plasma mass spectrometry (ICP-MS) method for the determination of migration Co，As，Br，Cd，Sb，Ba and Pb in recombinant human coagulation factor Ⅷ-Fc fusion protein for injection，and to quantitatively analyze the compatibility of long-term stored samples.

After adding 0.75 mL of water to the sample for 4 h，the purified water was filled to 5 mL，and the contents of 7 elements in the solution were determined by standard addition method. The working parameters of ICP-MS：radio frequency (RF) power of 1 550 W，sampling depth of 10.0 mm，carrier gas flow rate of 0.50 L·min^-1，atomizer pump speed of 0.30 r·s^-1，atomization chamber temperature of 2 ℃，dilution gas flow rate of 0.74 L·min^-1，repeated sampling times of 3 times，analysis mode of full quantitative.

The linear relationship of each element was good in the concentration range of the detected mass，and the recoveries of the element added were 92.0%-101.8%. When applied to the determination of the samples at each accelerated placement point，the increased migration amounts were 43.2，68.7 and 66.8 ng·mL^-1，respectively，except the element content of Br increased slightly. The contents of the remaining 6 elements were far below the prescribed limit.

The method is reliable and can be used for the determination of migration of 7 elements in recombinant human coagulation factor Ⅷ-Fc fusion protein for injection.

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 establish a microbial limit test method and quality standard conforms to the USP for compound Kushen extract and its related components.

Comparative analysis was conducted on the standards for traditional Chinese medicine preparations and decoction pieces in the USP and the Chinese Pharmacopoeia 2020 Edition to determine the microbial limit standards for compound Kushen extract and its related components. Then，guided by the General Principles of the USP<61> and <62>，a microbial limit test method suitable for compound Kushen extract and its related components was developed. The plate pouring method was used to perform a methodological applicability test on the total aerobic bacterial count，mold and yeast count of compound Kushen extract and its two components Sophorae Flavescentis Radix and Heterosmilacis Rhizoma. The method applicability test was conducted on the control bacteria using the direct inoculation method. Finally，the MALDI/TOF MS microbial identification method and bacterial 16S rRNA gene sequence alignment analysis method were comprehensively used to identify the bacterial species of the contaminated microorganisms in the sample，and further analysis was conducted on the distribution and harm of the contaminated microbial population.

As a result，microbial limit standards for compound Kushen extract and its related components were established in accordance with the requirements of the USP. The recoveries of the counting methods for compound Kushen extract and its two components，Sophorae Flavescentis Radix and Heterosmilacis Rhizoma，were between 0.5 and 2.0. The positive control strains in the control bacterial method suitability test were able to grow，meeting the requirements of the USP. According to the identification results，40 contaminated microorganisms involved 13 species and 5 genera，mainly covering different types of Bacillus genus (87.5%)，Enterobacterium genus (10%)，and Pseudomonas genus (2.5%). Polluting microorganisms were all less harmful conditional pathogenic bacteria.

Established a microbial limit test method and quality standard conforms to the USP for compound Kushen extract and its related components. Defined the distribution and harm analysis of the pollution microorganism poulation of the above products. Improved the microbial quality control of the Chinese medicine preparation and its components.