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 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 a pre-column derivatization high performance liquid chromatography-mass spectrometry to determine biogenic amines in osteopeptide injections and determine the changes of biogenic amines after the stability influence factor test and accelerated test.

The osteopeptide injections were separated by a ZORBAX SB-C₁₈ chromatographic column and gradient elution after derivatization by dansyl chloride. Ten kinds of biogenic amines was determined by mass spectrometry with electrospray ion source and multiple reaction monitoring in positive mode. The osteopeptide injections were placed under high temperature，strong light and accelerated experimental conditions to inspect the stability of biogenic amines.

Method validation showed that the linear relationship of 10 biological amines was good，and the correlation coefficients were higher than 0.990. The detection limits were 0.01-0.10 ng·mL^-1，the quantitation limits were 0.05-0.30 ng·mL^-1. Good accuracy，repeatability and durability were obtained. Under different conditions，the changes of biogenic amines in osteopeptide injections were significant. The accumulation of putrescine increased under high temperature，while spermine and spermidine decreased. The biogenic amines were unstable under strong light and accelerated test.

Method validation shows that the method can be applicable to simultaneous determine 10 biogenic amines in osteopeptide injections. It provided a reference to establish and improve the quality standards of biogenic amines in osteopeptide and other drugs. In addition，the research of the stability of biological amines shows that high temperature and strong light will affect the stability of biogenic amines. Therefore，quality control and supervision should be strengthened during drug production and storage to ensure the stability of drug.

To establish an HPLC analysis method for the determination of diazepam，nordiazepam and oxazepam in hair samples.

The determination of drug content and related substances was performed by high performance liquid chromatography (HPLC). Ultrasonic method combined with liquid-liquid extraction method was used as the pretreatment method. The chromatographic column was Athena C₁₈-WP column (250 mm×4.6 mm，5 μm)；the mobile phase was the mixture of methanol：0.02 mol·L^-1 sodium dihydrogen phosphate (adjusted to pH 3.4 with phosphoric acid)：acetonitrile (30:43:27，v/v/v) in an isometric elution；the column temperature was 50 ℃；the flow rate was 0.7 mL·min^-1；the running time was 30 min；the injection volume was 20 μL. The detection wavelength was 254 nm. The internal standard was clonazepam.

The linearity of all the analytes were good in the concentration range of 0.1 to 25 ng·mg^-1（r>0.995）. The limit of quantitative was 0.1 ng·mg^-1 and the limit of detection was 0.05 ng·mg^-1. The intra-batch accuracies were 88.2%-103.9% (n=6) and the inter-batch accuracies were 88.5%-106.2% with imprecisions ≤9.19%. The recoveries were stable for three anlytes，which met the requirement of methodology. The present method was applied to the authetic hair samples，in which the concentrations of diazepam，norazepam and oxazepam were (0.307±0.016) ng·mg^-1，(0.244±0.012) ng·mg^-1 and (0.478±0.053) ng·mg^-1 respectively. Besides，C_norazepam/C_diazepam was 0.795，which was in consistent with the literature reported.

The established HPLC method is fast and easy to operate，with good reproducibility，applicability，and reliability.

To establish a quantitative ¹H-NMR (qHNMR) method for the determination of dexzopiclone tablets content.

Proton signal at δ 6.08 of 1，3，5-trimethoxybenzene and δ 8.54，8.38，8.12，7.78 of dexzopiclone were served as the internal standard and quantitative peaks，respectively. DMSO-d₆ was employed as the solvent. The qHNMR spectra were acquired at 298 K with 10 s relaxation delay and 32 scanning times.

The content of dexzopiclone was estimated to be 2.94% （RSD=0.15%）by qHNMR method，which indicated that 3.00 mg of dexzopiclone was in one tablet. The result was consistent with the description of the label.

qHNMR method can be used to determine the content of dexzopiclone. The method is accurate，simple and efficient.

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 a method for determining the absolute contents of candesartan cilexetil and amlodipine besylate in candesartan cilexetil and amlodipine tablets by qNMR.

The chemical shift δ 5.51 of candesartan cilexetil and δ 5.31 of amlodipine besylate were used as the quantitative peaks. δ 6.27 of maleic acid was the quantitative peak of internal standard. DMSO-d₆ was used as the solvent.

The method was highly specific and the solvent peak，water peak and excipient peaks did not interfere with the quantitative peaks. Candesartan cilexetil showed a good linear relationship in the concentration range of 1.580 0- 9.480 2 mg·mL^-1，r=1.000，RSDs of precision，repeatability and stability were 0.070%，1.7% and 0.68%，respectively. The recoveries of low，medium and high concentration spiked were 98.1%-99.2%. The linear range of amlodipine besylate was 0.983 9-5.903 6 mg·mL^-1 (r=0.999 9). The RSDs of precision，repeatability and stability were 0.050%，1.8% and 0.79%，respectively. The recovery of amlodipine besylate was 99.1%-102.0%. This method was used to test two batches of reference preparations and one batch of sample from different sources. The results showed that the content of candesatan cilexetil was between 98.10% to 98.75%, and that of amlldipine besylate was between 98.98% to 99.60%.

This method is rapid and accurate and it is not necessary to use a single component reference substance. This method provides a new method to determine the content to candesartan cilexetil and amlodipine tablets.

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 develop the national standard materials of progesterone in frozen human serum and to evaluate the accuracy and standardization of serum progesterone detection kits.

Low and high concentrations of serum were from normal people and pregnant women individuals respectively，with a clear appearance，no obvious hemolysis，jaundice and lipid blood. After all tests for four infectious diseases were negative，thrombin，anhydrous calcium chloride and anhydrous sodium carbonate were added according to the proportion of 1 kU·L^-1，2.219 6 g·L^-1 and 2.65 g·L^-1 respectively，and centrifuged (4 000 r·min^-1，4 ℃，25 min) after fully mixing. After twice of multiple filtration and sterilization，serum pools were packed in ampoules to prepare candidates Ⅰ and Ⅱand stored at -70 ℃. Single factor variance method and linear regression method were used to evaluate the homogeneity and stability of the candidate. Five labs working together used reference method (isotope dilution liquid chromatography tandem mass spectrometry) to assign value for candidate. The uncertainty was calculated. At the same time，the commutability was evaluated.

Through statistical analysis, the F values of homogeneity for candidate Ⅰ and Ⅱ were 0.570 9 and 1.200 9, respectively, which were all less than F_0.05. Candidate Ⅰ and Ⅱ could be stable at least 8 h at 20-25 ℃. At 2-8 ℃, candidate Ⅰ and Ⅱ could be stable at least 33 d and 7 d respectively. Candidate Ⅰ and Ⅱ cound be stable at least 33 d at -20 ℃. Candidate Ⅰ and Ⅱ remained stable after repeated freeze-thaw cycles for 6 times. The assigned values were：candidate Ⅰ：(4.44±0.24) ng·mL^-1 (k=2), Ⅱ：(16.79±0.82) ng·mL^-1 (k=2). The determination results of candidate Ⅰ and Ⅱ were all within the 95% confidence interval of the fitting regression line established by the determination values of fresh serum samples.

Progesterone candidate had good homogeneity，stability，interoperability. It had accurate and reliable determination value，which could be used as national standard. The establishment of this national standard was of great significance for promoting the consistency and standardization of progesterone testing results.