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 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.

To establish a method for the determination of 22 mycotoxins in pharmaceutical excipients by ultra-high performance liquid chromatography-ion mobility time-of-flight mass spectrometry (UHPLC-IM TOF MS).

The samples were separated on a Waters CORTECS^® UPLC^® C₁₈(100 mm×2.1 mm，1.6 μm) column by gradient elution at a flow rate of 0.25 mL·min^-1 using 0.1% formic acid and a mixture of acetonitrile and methanol (60:40) as the mobile phase. The column temperature was maintained at 35 ℃. MSe data acquisition mode was chosen and electrospray ion source operating in the positive/negative ionization mode for data acquisition was applied. The external standard method was used for quantification.

22 mycotoxins showed good linear relationships within their respective ranges (r>0.998 5). The limits of detection were 0.1-2.0 μg·kg^-1. The recoveries of 22 mycotoxins at three levels were in the range of 80.4%-118.2%，and the RSDs were 0.20%-8.8%. The matrix effect of 22 mycotoxins was not obvious. The method was applied to the detection of 32 batches of corn starch and 167 batches of dextrin. Aflatoxin B1，fumonisins B1 and B2，and zearalenone were detected in some batches.

The method is accurate，efficient and stable. It can be used in quality control of mycotoxins in pharmaceutical excipients，and provides technical supports for the risk assessment of mycotoxins.

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 establish the ultra high performance liquid chromatography (UPLC) fingerprint of Qiye Shen’an dropping pills，and to determine the contents of 8 index components by quantitative analysis of multi-components by single marker at the same time.

Waters CORTECS^® T3 (150 mm×2.1 mm，1.6 μm) chromatography column was used for gradient elution with acetonitrile -0.1% phosphoric acid as mobile phase，flow rate was 0.40 mL·min^-1，column temperature was 35 ℃，detection wavelength was 203 nm.

The UPLC fingerprint of Qiye Shen’an dropping pills was established，8 common peaks were established，and the similarity of 15 batches of samples was greater than 0.99. Ginsenoside Rb₁，ginsenoside RC，panax notoginseng saponin FC，ginsenoside Rb₂，ginsenoside Rb₃，ginsenoside Rd，panax notoginseng saponin Fe and panax notoginseng saponin Fd were determined by quantitative analysis of multi-components by single marker method. The contents of 8 components in 15 batches were between 7.6-10.0 mg per pill. The average recoveries were 99.8%，100.6%，99.8%，101.2%，102.1%，101.9%，99.7% and 100.2% respectively，and the RSDs were 2.3%，2.2%，2.0%，1.5%，1.7%，1.2%，2.4% and 2.6% respectively.

The UPLC fingerprint of Qiye Shen’an dropping pills and the content determination method of quantitative analysis of multi-components by single marker method established in this study are simple to operation，and have good repeatability，stability and reliability，and can provide a more comprehensive basis for the quality control of Qiye Shen’an dropping pills.

To establish a method for determination of 7 mycotoxin contaminants in Jianqu by ultra high performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS）.

The samples were extracted with acetonitrile aqueous solution (containing 0.1% formic acid) ，and purified by QuEChERS extraction salt bag and Oasis PRiME HLB solid phase extraction column. The column of UPLC was WATERS HSS T3（100 mm×2.1 mm，1.8 μm）. Mobile phase was acetonitrile-5 mmol·L^-1 ammonium formate solution (containing 0.1% formic acid) with gradient elution. Ionization mode was electrospray ionization(ESI) with positive mode. The work mode was multiple-reaction monitoring mode(MRM).

The developed method provided a good linearity for the 7 mycotoxins with their respective linear rangers. The correlation(r) ranged from 0.999 1 to 0.999 9. The average recoveries ranged from 83.5% to 113.8%，RSDs of 2.1% to 5.2%. Among 10 samples were selected for analysis，aflatoxin B1 was detected from 3 samples at concentration of 1.32 μg·kg^-1 to 6.15 μg·kg^-1. The results indicated that there were serious safety risks in the Jianqu products.

This paper establishes a method for the determination of 7 mycotoxins in Jianqu. The residual of mycotoxins in Jianqu can be rapid ly detected by UPLC-MS/MS which is suitable for the risk monitoring of mycotoxins in Jianqu. This article reveals the current situation of mycotoxins contamination in Jianqu，providing a research basis for the safety control of traditional Chinese medicine. It is recommended that the relevant departments should strengthen the corresponding supervision work.

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 evaluate the processing ability of identification，tracing and abnormal occurs in drug manufactures by the proficiency testing for microbiological identification and traceability in Shandong Province.

The proficiency test was derived from an event of drug microbial contamination，and samples including contaminated products group and production group were designed to evaluate the testing and tracing competence of 264 participants from those aspects of drug control，identification，genetic comparison and traceability. The contaminated products group was composed of five simulated samples including one positive sample which included Enterobacter cloacae and Staphylococcus aureus，and four negative samples which were sterile. The production group was composed of five simulated samples including four positive samples and one negative sample，but each of the four positive sample included only one strain of Enterobacter cloacae，Staphylococcus aureus，Staphylococous epidemidis and Pseudomons aeruginosa，respectively.

259 participants reported their results. The rate of unqualified，qualified，good and excellent results were 3.5%，49.8%，46.7% and 0，respectively. But four results reported phylogenetic tree based on 16S rRNA gene without genetic comparison at the strain level. The unqualified result indicated inaccurate inspection of positive and negative sample. The qualified result indicated accurate inspection but inaccurate species identification or not. The good result showed accurate species identification without effective tracing analysis.

The ability of most drug manufactures to contaminant microorganisms testing are acceptable. But the ability of microbiological identification and traceability，the precise judgement and the effective measures to an emergency of microbial contamination in drugs remain to be strengthened.

To establish a method for related substances determination in timolol maleate by ultra-high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry（UPLC-Q/Orbitrap HRMS），by which the impurities both in active pharmaceutical ingredients（APIs） and preparations can be recognized and determined.

An ACE Excel3 C₁₈-AR column（150 mm×4.6 mm，3 μm）was used for the separation and a mixture of 0.01 mol·L^-1 ammonium acetate solution with 0.02% formic acid and methanol was employed as the mobile phase by gradient elution，at a flow rate of 0.6 mL·min^-1. The detection wavelength for UV detector was 295 nm，an HESI（heated ESI）ion source was employed in both the positive mode and negative mode. The possible fragmentation patterns prediction was conducted with the help of Mass Frontier 8.0 and Compound Discover 3.3. The related substances could be recognized and determined by means of the forced degradation of the APIs，with the calibration by the correction factors and confirmation by the mass spectrum data from UPLC-Q/Orbitrap HRMS.

The timolol impurity B[3-(tert-butylamino)-2-(4-morpholino-1，2，5-thiadiazol-3-yloxy)propan-1-ol]，timolol impurity D(4-morpholino-1，2，5-thiadiazol-2-ol)，timolol impurity E((S，Z)-4-(｛1-(tert-butylamino)- 3-[(4-morpholino-1，2，5-thiadiazol-3-yl) oxy] propan-2-yl｝oxy)-4-oxobut-2-enoic acid maleate salt) and timolol impurity C[N-(tert-butyl)-2，3-bis (4-morphloline-1，2，5-thiadiazol-3-yloxy) propan-1-amine maleate] were produced from the APIs under selected conditions and separated well in the specified HPLC condition，the limit of quantitation was 0.05 μg·mL^-1 and the limit of detection was 0.015 μg·mL^-1 for HPLC-UV. The contents of individual impurities were between 0.000 4%-0.09% and the results of total impurities were between 0.02%-0.12% for the samples from 4 different manufactures. The probable chemical structures of the 6 unspecified impurities were speculated according to the fragmentation pattern of fragment ions，combined with the fragment information，chemical structure of API and the references.

The system solution can be obtained by the degradation of the API，and be implied in the impurity analysis for the timolol maleate. The results can be used as a reference for the quality control of timolol maletae.

To establish a method and validate its feasibility for quality evaluation of Erycibes Caulis and its processed products，and analyze the effect on the contents of the seven active ingredient before and after processing.

The contents of components were determined by ultra performance liquid chromatography (UPLC). Chlorogenic acid was chosen as the internal reference substances，the relative correction factors (RCFs) of neochlorogenic acid scopolin，scopoletin，isochlorogenic acid B，isochlorogenic acid A，isochlorogenic acid C and to chlorogenic acid were established. The contents of these seven active ingredients were determined by external standard method and quantitative analysis of multi-components by single-marker (QAMS) method. The method was evaluated by comparison of the quantitative results between external standard method and quantitative analysis of multi-components by single-marker (QAMS).

The peaks of neochlorogenic acid，scopolin，chlorogenic acid，scopoletin，isochlorogenic acid B，isochlorogenic acid A and isochlorogenic acid C in the sample showed good linear relationship between 0.028-1.420 μg·μL^-1，0.019-0.956 μg·μL^-1，0.027-1.324 μg·μL^-1，0.014-0.720 μg·μL^-1，0.017-0.824 μg·μL^-1，0.010-0.500 μg·μL^-1 and 0.013-0.672 μg·μL^-1，respectively. The average recoveries of them（n=6）were as follows 98.9%，99.0%，100.6%，101.2%，100.8%，101.7% and 100.5%，with the RSDs of 1.1%，1.7%，1.5%，1.6%，0.55%，1.6% and 1.5%，respectively. It was showed that no significant difference was found in the quantitative results of seven ingredients by external standard method and QAMS method. The content of 5 kinds of organic acids (neochlorogenic acid，chlorogenic acid，isochlorogenic acid B，isochlorogenic acid A and isochlorogenic acid C) in Erycibes Caulis with different processing technology showed the same change trend. The sample of Y₅ (boiled products with licorice sauce and brine) had the highest contents，and the sample of Y₁₀ (dried products Ⅱ soaked in licorice sauce and brine) had the lowest. The content of scopoline was the highest in Y₅(3.53 mg·g^-1)，while the lowest was Y₁₀(0.31 mg·g^-1). The content of scopoletin in Y₇(dried products Ⅰ with licorice sauce) was the highest(1.48 mg·g^-1) and that in Y₃(boiled products Ⅱ with licorice sauce) was the lowest(0.30 mg·g^-1).

The RCFs established in the QAMS methods with chlorogenic acid as the internal reference substances is accurate and feasible. It can be used to control the quality of Erycibes Caulis. Both heating and excipients preparation have a certain effect on the active ingredients in Erycibes Caulis.