To establish a liquid-liquid extraction method for the determination of genotoxic impurities N-nitrosodimethylamine（NDMA） and N-nitrosodiethylamine（NDEA） in chondroitin sulfate sodium by gas chromatography-mass spectrometry (GC-MS).

The chromatographic column was Thermo TG WAXMS (30 m × 0.25 mm，0.25 μm）. The column temperature was maintained at 40 ℃ for 1 min，increased to 240 ℃ at 25 ℃·min^-1 and maintained for 2 min. The inlet temperature was 220 ℃. The carrier gas was high-purity helium，and the flow rate was 1.0 mL·min^-1. The ion source of mass spectrometry was EI source. The electron energy was 70 eV. The ion source temperature was 280 ℃ and the transmission line temperature was 240 ℃. Injection volume was 1 μL.

The LOD of NDMA was 0.64 ng·mL^-1. Experiment showed a good linear relationship between peak area and concentration in the range of 4-16 ng·mL^-1，and the correlation r was 0.999 3. The LOD of NDEA was 0.176 ng·mL^-1 with a good linear relationship between peak area and concentration within the range of 1.1-4.4 ng·mL^-1. The correlation r was 0.999 6. NDMA and NDEA were not detected in chondroitin sulfate sodium.

The method is simple，specific and can be used to determine the genotoxic impurities NDMA and NDEA in chondroitin sulfate sodium.

To establish an HPLC method for the determination of six related substances in N-fluorenylmethoxycarbonyl-O-tert-butyl-L-threonine.

The analysis was conducted on YMC Triart C₁₈(250 mm×4.6 mm，3μm) column，the mobile phase was consisted with 0.1% trifluoroacetic acid in water（A） and 0.1% trifluoroacetic acid in acetonitrile（B）at the flow rate of 1.0 mL·min^-1. The column temperature was set 30 ℃，the detection wavelength was 265 nm and the injection volume was 10 μL.

N-Fluorenylmethoxycarbonyl-O-tert-butyl-L-threonine had good separation from the adjacent impurity peaks；The resolution of impurity1- 6 was greater than 1.5，and showed a good linear relationship (r≥0.999) in the corresponding mass concentration range，the detection limit of impurity 1-6 was 0.03 μg·mL^-1，and the quantitative limit was 0.06 μg·mL^-1，the average recovery rate (n=9) of impurity 1-6 was in the range of 97.6%-98.8%. The results of the three batches of N-fluorenylmethoxycarbonyl-O-tert-butyl-L-threonine showed that the contents of impurity 2，impurity 4 were <0.2% and <0.1%，respectively，and the other four impurities were not detected，and content of the total impurity was <1%.

This method has good resolution，high sensitivity and strong specificity，and is suitable for the determination of related substances in N-fluorenylmethoxycarbonyl-O-tert-butyl-L-threonine.

To establish a method for determination of gas impurities in medical gases.

The study introduced the principle and measurement system of gas detector tubes，and researched on the accuracy，precision and influence factors. The method was applied to the detection of gas impurities in medicinal gases.

The test results showed that the compressed gas detection tubes produced by manufacturer A and manufacturer B were greatly affected by the pressure. The compressed gas detection tubes produced by manufacturer A and manufacturer C and the ambient gas detection tubes of all manufacturers were greatly affected by the flow rate. All the gas detection tubes were affected by the measurement time. Both ambient temperature and humidity can affect the detection of H₂O detection tube，and ambient humidity also has an impact on the CO₂ ambient gas detection tube produced by manufacturer B. The difference between different manufacturers’ detection tubes was indistinct under the same testing conditions. The compressed gas detection tubes can accurately measure the gas impurity content under the continuous flow measurement system，while some ambient gas detection tubes can not accurately measure. The impurity interference was different for the detection tubes with different principles. It is suggested that the influencing factors should be paid attention to when the gas detection tubes are used，and the appropriate detection tubes and method should be selected.

The gas detector tubes can be used in the detection of medical gases with good accuracy and precision. This study provides references for the detection of impurities in medical gases.

To study the correlation between heavy metal and harmful elements of Jasmine and the geo-authenticity，and to evaluate the risk.

The content difference of heavy metal elements in 43 batches of Jasmine from different production areas was determined by ICP-MS，and cluster analysis was carried out to study the correlation between the content of each element in Jasmine and the geo-authenticity. The dissolution rate of each element after decocting in water was determined，the symbolic elements that might affect the contents of heavy metal and harmful elements was screened，and risk assessment was performed.

The copolymerization of 43 batches of jasmine from different producing areas was divided into 2 types. The contents of heavy metals in powder and dry paste of Jasmine from different producing areas declined in the order of Cu，Cd，Pb ，As and Hg，and the content of Cu in powder and dry paste was higher than other elements. The dissolution rates of heavy metal and harmful elements declined in the order of As，Pb，Hg，Cu and Cd，and Pb，Cd and As were the representative elements that might affect the content of heavy metal and harmful elements in Jasmine. Risk assessment showed that MOE_Pb<1 existed in samples from Hengzhou Town，Hengzhou City，Guangxi Province (batch number：20200810) and Quanzhou City，Fujian Province (batch number：20230705)，and the hazard index and exposure limit values in other producing areas were in line with the limit standards.

This paper provides scientific basis for selection of planting area，artificial breeding and formulation of heavy metal and harmful limit standard.

Based on a sequential analysis method of “physicochemical properties-main component content-fingerprint similarity-anaphylactoid reaction”，the stability and safety of Danhong injection with commonly used clinical solvents 0.9% sodium chloride and 5% glucose injections were evaluated.

According to the clinical application，Danhong injection was mixed with 0.9% sodium chloride injection or 5% glucose injection in the ratios of 20 mL：100 mL，30 mL：100 mL，40 mL：100 mL and 30 mL：250 mL，40 mL：250 mL，respectively. Then，they were placed at room temperature within 10 h. The properties，osmotic pressure，insoluble particles and pH value in the solutions were observed or measured at different time points. The contents of the main components at different time points were determined. The HPLC and ¹H NMR fingerprints at different time points were analyzed by similarity evaluation. The in vitro anaphylactoid reaction assay of RBL-2H3 cell degranulation was used to evaluate the safety of the mixture solutions.

The properties，osmotic pressure，insoluble particles and pH value of solutions were stable within 10 h after mixing，and there was no significant difference in the contents of the main components. The HPLC and ¹H NMR fingerprints showed good similarity，and the mixture solutions didn’t induce obvious degranulation in RBL-2H3 cells.

In this study，the comprehensive evaluation from the physical，chemical and biological perspectives showed that in the concentration range of 30 mL：250-40 mL：100 mL，Danhong injection combined with 0.9% sodium chloride injection or 5% glucose injection had good stability and safety within 10 h，which provides evidences for the clinical practice.

To establish an high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of 45 additives in oral liquid preparations of traditional Chinese medicine.

The samples were ultrasonically extracted by acetonitrile-methanol (9:1) (containing 0.1% formic acid). The separation was carried out on an Agilent Eclipse Plus C₁₈ chromatographic column (150 mm×3.0 mm，1.8μm) using gradient elution of methanol -5 mmol·L^-1 ammonium acetate. The compounds were scanned and detected simultaneously by electrospray ionization（ESI）ion source in both positive ion and negative ion mode under dynamic multiple reaction monitoring. The retention time and ion ratio were used for qualitative analysis and the external standard method was adopted for quantification.

The good linear relationship of peak area was observed for the 45 additives with correlation coefficients ≥0.992 in the concentration range of 5-2 000 ng·mL^-1，and the limits of quantitation were between 0.2 mg·kg^-1 and 4.0 mg·kg^-1 under the above chromatographic and mass spectrometric conditions. The average recoveries of the blank samples at different added levels ranged from 75.4% to 118.4% with RSDs of 0.70%-9.8%. The method was used to detect 20 batches of oral liquid preparations of traditional Chinese medicines purchased from pharmacies. Benzoic acid was detected in 6 batches with the contents of benzoic acid from 0.13% to 0.27%，and sorbic acid，trans-cinnamic acid，molasses，ethyl 4-hydroxybenzoate，acesulfame potassium，dehydroacetic acid and saccharin sodium were detected in 7 batches of samples respectively.

The established high-throughput detection method is sensitive，simple and fast in pre-treatment，with high accuracy，stable recovery and reduced detection cost effectively. It can be used for the simultaneous rapid screening of multiple additives in oral liquid preparations of traditional Chinese medicine.

To establish the fingerprint of Panax quinquefolius L. from Shandong by UPLC-PDA，and to simultaneously determine the contents of 16 ginsenosides.

The chromatographic column was an Acquity UPLC BEH C₁₈ column(50 mm×2.1 mm，1.7 μm)，which was eluted with water-acetonitrile by gradient at a flow rate of 0.4 mL·min^-1. The detection wavelength was 203 nm，the column temperature was 30 °C，and the injection volume was 2 μL. The Chinese Pharmacopoeia “Chinese Medicine Chromatography Fingerprint Similarity Evaluation System (2012 Edition)” was used for evaluation，and 42 batches of Panax quinquefolius L. from different habitats were compared with cluster analysis and principal component analysis.

The total content 16 ginsenosides in Panax quinquefolius L. from in Shandong were 19.73-58.07 mg·g^-1，and the average value was (34.72±8.22) mg·g^-1. The fingerprints of the ginsenosides in Panax quinquefolius L. from Shandong were established，and the similarities were above 0.90. And 10 common peaks constituted the characteristic peaks of Panax quinquefolius L.. Cluster analysis and principal component analysis showed that the contents of ginsenosides in Panax quinquefolius L. from Shandong were stable.

The fingerprint of Panax quinquefolius L. established is highly characteristic，and the method issimple，which provides data support for the identification and quality control of Panax quinquefolius L..

To establish a UHPLC method for simultaneously determining sinomenine，neochlorogenic acid，magnolflorine，cryptochlorogenic acid，chlorogenic acid，isochlorogenic acid B，isochlorogenic acid A，isochlorogenic acid C，harpagoside，ligustilide and ammonium glycyrrhizate in Jinteng Qingbi granules，and evaluate the quality of Jinteng Qingbi granules combined with principal component analysis.

UHPLC wavelength switching method was employed in the study. The chromatographic separation was performed on a Waters XSelect^® CSH C₁₈ column (150 mm×4.6 mm，2.5 μm) using methanol-acetonitrile (1:1) as mobile phase A and 0.2% phosphoric acid aqueous solution as mobile phase B in a gradient mode at 25 ℃. The flow rate was 1.0 mL·min^-1，and the UV detection wavelength was chosen at 218 nm for sinomenine during 0-17 min，326 nm for neochlorogenic acid，cryptochlorogenic acid，chlorogenic acid，isochlorogenic acid B，isochlorogenic acid A and isochlorogenic acid C during 17-25 min and 34-98nm，263 nm for magnolflorine，harpagoside，ligustilide and ammonium glycyrrhizate during 25-34 min and 98-125nm，respectively. Furthermore，multiple statistical analysis was conducted on the contents of 11 components in 20 batches of Jinteng Qingbi granules using SPSS27.0 software.

Satisfactory linearities of sinomenine，neochlorogenic acid，magnolflorine，cryptochlorogenic acid，chlorogenic acid，isochlorogenic acid B，isochlorogenic acid A，isochlorogenic acid C，harpagoside，ligustilide and ammonium glycyrrhizate were in the ranges of 14.36-143.61 μg·mL^-1 (r=0.999 9)，7.71-77.15 μg·mL^-1 (r=0.999 8)，9.18-91.83 μg·mL^-1 (r=0.999 7)，10.71-107.07 μg·mL^-1 (r=0.999 8)，12.88-128.80 μg·mL^-1 (r=0.999 8)，5.20-51.95 μg·mL^-1 (r=0.999 7)，5.18-51.84 μg·mL^-1 (r=0.999 8)，5.40-53.95 μg·mL^-1 (r=0.999 8)，2.62-26.16 μg·mL^-1 (r=0.999 9)，6.31-63.06 μg·mL^-1 (r=0.999 9) and 11.13-111.26 μg·mL^-1 (r=0.997 6)，respectively. The average recoveries (n=6) were 98.3%，98.3%，98.5%，98.9%，99.2%，101.0%，98.1%，97.1%，96.8%，98.0% and 98.7%，respectively，with RSDs less than 3.0%. The contents ranges of sinomenine and other 10 components of 20 batches of Jinteng Qingbi granules samples were 2.206-2.704，1.071-1.403，2.096-2.487，1.321-1.724，2.241-2.612，0.605-0.749，0.363-0.412，0.835-1.020，0.151-0.191，0.791-1.188 and 1.008-1.363 mg·g^-1，respectively. The results of principal component analysis showed that the quality differences between batches of continuously produced Jinteng Qingbi granules were relatively smaller，and the comprehensive quality of samples S1，S5 and S7 was relatively better.

The established UHPLC method of multi-index component determination is simple，accurate and stable. Combined with principal component analysis，it can be used for quality evaluation of Jinteng Qingbi granules comprehensively.

To establish a quality consistency assessment method to evaluate the consistency of product quality of Liuwei Dihuang concentrated pills (LDCP) among different manufacturers.

Firstly，high performance liquid chromatography (HPLC) was used to determine the content of the six index components in LDCP，and analyze the content differences between different batches of the same manufacturer and the current product quality of different manufacturers. Secondly，quality consistency parameters，i.e.，intra-batch content consistency differences (P_A)，inter-batch content consistency differences (P_B)，and fingerprint similarity (P_C)，were constructed to assess the consistency of product quality among the different manufacturers. And lastly，the consistency parameters were taken as the variables and subjected to the principal component analysis (PCA) to classify the consistency of the LDCP samples of the seven manufacturers to be fitted and differentiated.

The contents of the six index components in thirty-five batches of LDCP samples from seven manufacturers totaled 1.48-2.99 mg per pill，the RSDs of the contents of different components were 4.9%-29.7%，and the consistency parameters of the seven products were 4.2%-15.1% for P_A，26.4%-49.5% for P_B，and 92.9%-98.2% for P_C. There were some differences in the homogeneity of contents in samples from different manufacturers，and the contents of the product varied significantly between batches，with P value of 64.5-75.8，indicating that the difference in the consistency of samples from different manufacturers was relatively small. But under certain conditions，the seven manufacturers can be classified into three categories，with B and J as a category，Z and R as a category，and X，F，and S as a category.

This study provides a simple and effective method for monitoring and distinguishing the quality consistency of commercially available LDCP products，and the experimental results can provide a reference for the sample quality homogeneity of LDCP manufacturers.

To evaluate the quality of the Japanese encephalitis inactivated vaccine strain adapted in human diploid cells (ZFB-3).

The virus strain was identified by identification test to determine whether it was Japanese encephalitis virus strain，the virus titer was tested in mice brain to evaluate the adaptability and proliferation ability of the virus seed on human diploid cells (ZFB-3)，the sterility test，mycoplasma test，and external virus factor test was conducted for any external contamination.

The virus strain was proved as Japanese encephalitis virus and had been well adapted to human diploid cells (ZFB-3) with high virus titer. The virus strain was free from contamination by bacteria，fungi，mycoplasma or exogenous viral factors.

The quality of Japanese encephalitis inactivated vaccine strain adapted in human diploid cells (ZFB-3) meets the requirements and can be applied to vaccine production.