To establish a simple and practical microbiological counting method suitable for sheet drug packaging materials by comparing the results of four sampling methods.

The samples of artificial contamination of sheet drug packaging materials were prepared by standard strain adding method. The surface microorganisms were collected by wiping method prescribed by national drug packaging container (material) standard, as well as by self-designed washing method, direct inoculation method and contact dish method. The corresponding recovery rate was calculated. The results of 4 sampling methods were analyzed by one way analysis of variance (ANOVA).

From high to low, the recovery rate was as follows: contact dish method, direct inoculation method, wiping method and washing method. There were significant differences in the recovery rates of contact dish method, wiping method and washing method (P<0.05). The recovery rate of contact dish method was slightly higher than that of direct inoculation method, but there was no significant difference between them (P>0.05). There was no significant difference in the recoveries of medicinal film, aluminum foil and hard sheet among the four methods (P>0.05).

The contact dish method is simple, sensitive and accurate, and can be used for the examination of the microbial limit counting method of sheet drug packaging materials.

The early warning of new psychoactive substance iso-propoxate (homologue of etomidate) was carried out through sewage drug monitoring technology, and quantitative research was conducted to provide technical support for management and law enforcement.

The abnormal results were obtained by quantitative analysis of multiple reaction monitoring (MRM) mode using online solid phase extraction-ultra high performance liquid chromatography tandem mass spectrometry (SPE-UPLC-MS/MS), and the basic information of abnormal substance was determined by precursor ion scanning mode. The qualitative determination was carried out using parallel reaction monitoring (PRM) mode by ultra high performance liquid chromatography quadrupole-orbitrap high resolution mass spectrometry (UPLC-Q exactive HRMS) after the directional synthesis of the compound. Quantitative study was then conducted by commercial reference products. The correlation analysis was carried out by SPSS 27.

The abnormal substance was determined to be iso-propoxate. The optimized MRM parameters could be distinguished from its isomers by specific ion abundance ratio. The correlation analysis of quantitative results showed that it was similar to etomidate and ketamine abuse areas.

In the process of sewage drug monitoring, it is necessary to pay attention to the proportional relationship between prototype and metabolite. It is important to summarize the characteristic fragments and characteristic neutral loss information of specific types of compounds, carry out screening non-targeted detection for key samples in key areas in the monitoring process, and analyze potential substances using high-resolution mass spectrometry and other methods, so as to fully leveraging the early warning role of sewage drug monitoring.

To establish an HPLC characteristic chromatogram for Hyssopus cuspidatu Boriss. and control quality and identity authentication for the herb.

The HPLC method was used, and the mobile phases were acetonitrile (A) and 0.1% aqueous phosphoric acid (B) in gradient elution(0-15 min, 10% A; 15-30 min, 10% A→15% A; 30-40 min, 15% A→18% A; 40-60 min, 18% A→23% A; 60-70 min, 23% A→55% A; 70-85 min, 55% A→60% A; 85-85.1 min, 60% A→10% A; 85.1-90 min, 10% A). The column temperature was 30 ℃, the flow rate was 1.0 mL·min^-1, the detection wavelength was 330 nm and the injection volume was 20 μL. Fifteen batches of Hyssopus cuspidatu Boriss. and its adulterants, notably Cynanchum officinale, were analyzed to construct characteristic chromatogram. The authenticity and quality of Hyssopus cuspidatu Boriss. were assessed through principal component analysis(PCA), cluster analysis, and similarity analysis.

Analysis of the characteristic chromatogram of ten Hyssopus cuspidatu Boriss. batches revealed fifteen distinct peaks, with six compounds identified as isodendrobioside, molluscoside, rosmarinic acid, salvianolic acid, geranylgeranyl, and trichothecenes. Cluster analysis segregated the Hyssopus cuspidatu Boriss. samples into three distinct groups, primarily influenced by geographical (latitude and longitude) and environmental (climate) factors. PCA results indicated that four principal components accounted for 92.914% of the variance. The similarities for the ten batches of Hyssopus cuspidatu Boriss. ranged from 0.896 to 0.997, with no significant difference observed between the wild and cultivated varieties in terms of overall HPLC profile and relative peak content. The overall profiles of the HPLC characteristic chromatogram and the contents of the main components of the Hyssopus cuspidatu Boriss. and the Nepeta bracteata Benth. were significantly different.

The HPLC characteristic chromatogram method developed in this study is reproducible, stable, and practical for the quality control and authentication of Hyssopus cuspidatu Boriss. Moreover, it offers a reliable analytical technique for the quality evaluation and authentication of this herb, providing substantial data support.

To study different batches of Xiaoer Resuqing granules by combining the method of fingerprint, multi-index component content determination and chemical pattern recognition analysis technology, and to provide the basis for its quality evaluation.

The chromatographic SuperLu C₁₈(250 mm×4.6 mm, 5 μm) column was adopted with mobile phase composed of methanol (A)-0.1% phosphoric acid (B) with gradient elution at a flow rate of 1.0 mL·min^-1. The column temperature was 30 ℃, and the detection wavelength was 280 nm. Eleven characteristic components were identified, and the contents of seven active components, including puerarin, forsythiaside A, phillyrin, baicalin, wogonoside, baicalein and wogonin were determined. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were used to classify 15 batches of samples, and orthogonal least partial squares discriminant analysis (OPLS-DA) was performed. To screen out the difference components between batches of Xiaoer Resuqing granules.

The HPLC fingerprint of Xiaoer Resuqing granules and the content determination method of 7 components were established, the results of the two methods met the requirements. Twenty-eight common peaks were identified, 11 chromatographic peaks were identified, and the similarities of 15 batches of samples ranged from 0.995 to 0.999. HCA and PCA results showed that 15 batches were clustered into two categories, and OPLS-DA screened out 13 markers that caused the differences among the 15 batches of samples. There was little difference in the contents of ingredients.

The established HPLC fingerprint of Xiaoer Resuqing granules and the determination method of 7 components are specific, accurate and reliable. Combined with chemical pattern recognition, it can be effectively used for the quality control of Xiaoer Resuqing granules.

To determine the in vitro release degree of musk sustained-release mini-tablets by reciprocating cylinder method.

Gas chromatography was used to establish the in vitro analysis of muscone, which is the main active ingredient of sustained-release mini-tablets. Comparing its equilibrium solubility in different concentrations of Tween-80, hexadecyl trimethyl ammonium bromide (CTAB) and sodium dodecyl sulfate (SDS), to determine the type of release medium. The effects of residence time, drip time, reciprocation rate, and screen mesh sizes on the release behaviours of muscone were investigated. Results were compared with that of the paddle method. Meanwhile, a preliminary investigation into the mechanism of its release was also carried out.

The linearity of the constructed analytical method was better, the RSD values of precision, repeatability and stability were less than 3%, and the spiked sample recovery was qualified. The release medium for the reciprocating cartridge method was 200 mL of 0.05% Tween-80, with a dwell and drip time of 20 s, a reciprocation rate of 15 dip·min^-1, and upper and lower screen mesh sizes of 20 and 40 respectively. Compared with the paddle method, Muscone was completely released under different pH conditions in the reciprocating cylinder method, and the release curve increased smoothly.

The study can provide some references for the reciprocating cylinder method in the in vitro evaluation of sustained-release prescriptions of traditional Chinese medicine.

To develop a method for characterizing in vitro release of cyclosporine ophthalmic emulsion.

The Franz diffusion cell and the polyvinylidene fluoride membrane were adopted with buffer-ethanol (40∶60) as receiving media. The sampling time was set at 60, 125, 190, 255, 320, 385 min, respectively.

The in vitro release method showed that the inertia of membrane, specificity, sensitivity and selectivity met the requirements. The validation of HPLC showed that the quantitative limit of the method was 0.07 μg·mL^-1 and a good linear relationship between the concentration range of 0.07-44.62 μg·mL^-1. The average recovery was 98.9%. Compared with the original preparation by FDA guideline, the in vitro release of the self-developed preparation was the same as the reference preparation.

This method is suitable for the in vitro release evaluation of cyclosporine eye drops.

To establish a stable and reliable gas chromatography-tandem mass spectrometry method for the determination of N-nitrosodimethylamine (NDMA) in metformin hydrochloride sustained-release tablets, and to optimize extraction conditions by investigating the effects of isopropyl alcohol and thioglycerin on the stability of the tested solution.

Separation was achieved on AB-InoWax capillary column (30 m×0.25 mm×0.25 μm) with polyethylene glycol as the stationary phase. Electron ion(EI) source and multiple reaction monitoring (MRM) mode were used. Quantitative determination was performed by both external standard and internal standard.

The addition of thioglycerin could significantly improve the stability of the test solution. NDMA showed good linearity within the concentration range of 0.25-50 ng·mL^-1(r>0.999). The detection limit of the method was 0.1 ng·g^-1 and the quantification limit of the method was 0.2 ng·g^-1. The average recoveries (n=9) were 97.3% and 94.9% while using external standard and internal standard, respectively. Precision, repeatability and stability were good with RSD less than 8%. Ninety batches of metformin hydrochloride sustained release tablets were tested. NDMA content in all detected samples were all less than 30% of the acceptable limit set by the National Medical Products Administration and FDA.

This method shows satisfactory sensibility, specificity, accuracy, stability and durability, which is suitable for quantitative analysis of NDMA in metformin hydrochloride sustained-release tablets, providing technical support for the quality and safety of related products.

To optimize the content determination method of morphine sulfate suppositories, which had high toxicity of extraction solvent and poor specificity and generality of chromatographic conditions.

The optimization of the preparation method for the test solution was to prepare the test solution by ice bath freezing and n-heptane extraction, and to compare the content determination results of the test solution prepared by the United States Pharmacopeia method (extracted with trichloromethane). The optimization of chromatographic conditions for content determination was based on the comprehensive comparison of United States Pharmacopeia, British Pharmacopeia and YBH specification. Symmetry C₁₈ column (150 mm×4.6 mm, 5 μm) was finally used. The mobile phase was 0.01 mol·L^-1 potassium dihydrogen phosphate solution containing 0.202% sodium heptane sulfonate (containing 0.1% triethylamine, adjusted to pH 2.5 with phosphoric acid) -methanol (70∶30). The flow rate was 1.0 mL·min^-1. The column temperature was 30 ℃. The detection wavelength was 284 nm. The injection volume was 20 μL.

The content measured by ice bath freezing method was relatively low, while the content measured by n-heptane extraction and trichloromethane extraction was basically consistent, indicating that n-heptane could be used as extraction solvent instead of halogenated alkane. The linear range of morphine sulfate was 2.12-105.94 μg·mL^-1(r=0.999 9), and the LOQ was 10.60 ng. The RSD values of system precision, repeatability, intermediate precision and stability were all less than 2%. The average recoveries were 98.6%-99.6% and RSD was 0.21%-0.66%. After forced degradation, the main peak of the tested solution could be separated from the degraded impurities, with good specificity. By changing the flow rate, column temperature, pH value, mobile phase ratio and column brand, the main peak could be well separated from each impurity peak, with good robustness.

This study optimized the determination method for morphine sulfate suppositories. The preparation of the test solution used n-heptane instead of the highly toxic haloalkane, and meanwhile improved the chromatographic conditions, enhanced the environmental protection, specificity and applicability of the method. It can be used for the content determination of morphine sulfate suppositories.