To establish an HPLC method for simultaneous determination of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, forsythiaside A, 3，4-O-dicaffeoylquinic acid, 3，5-O-dicaffeoylquinic acid, 4，5-O-dicaffeoylquinic acid, forsythin, andrographalide and dehydroandrographalide in compound Shuanghua tablets.

The samples were extracted with 50% methanol solution under ultrasonic condition, and were performed on Agilent Zoabax SB-C₁₈ column (250 mm×4.6 mm, 5 μm) by gradient elution of acetonitrile -0.15% phosphoric acid solution at a flow rate of 1.0 mL·min^-1. The column temperature was 30 ℃, the injection volume was 10 μL, and the detection wavelength were set at 327 nm (detecting neochlorogenic acid，chlorogenic acid, cryptochlorogenic acid, forsythiaside A，3，4-O-dicaffeoylquinic acid，3，5-O-dicaffeoylquinic acid and 4，5-O-dicaffeoylquinic acid) and 226 nm (detecting forsythin, andrographalide and dehydroandrographalide).

The linear ranges of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid，forsythiaside A，3，4-O-dicaffeoylquinic acid, 3，5-O-dicaffeoylquinic acid, 4，5-O-dicaffeoylquinic acid, forsythin, andrographalide and dehydroandrographalide were 4.071-40.71 μg·mL^-1(r=0.999 9), 20.16-201.6 μg·mL^-1(r=0.999 9), 4.730-47.30 μg·mL^-1(r=0.999 9), 4.536-45.36 μg·mL^-1(r=0.999 8), 1.817-18.17 μg·mL^-1(r=0.999 9), 2.266-22.66 μg·mL^-1(r=0.999 7), 3.321-33.21 μg·mL^-1(r=0.999 9), 3.462-34.62 μg·mL^-1(r=0.999 6), 2.111-21.11 μg·mL^-1(r=0.999 9) and 2.290-22.90 μg·mL^-1(r=0.999 7), respectively. The average recoveries (n=6) were 101.3%(2.1%)，103.0%(1.5%)，100.9%(2.0%)，101.1%(2.0%)，98.4%(1.6%)，102.2%(2.4%)，98.2%(1.3%)，97.8%(2.0%)，99.0%(2.0%) and 96.4%(1.1%), respectively. The contents of the 10 components in 4 bacthes of Fufang Shuanghua tablets were in the range of 1.685-2.649 mg·g^-1, 12.202-13.780 mg·g^-1, 2.415-2.594 mg·g^-1, 1.340-1.919 mg·g^-1, 0.501-0.791 mg·g^-1, 0.891-1.342 mg·g^-1, 1.299-2.105 mg·g^-1, 1.147-1.504 mg·g^-1, 0.654-0.694 mg·g^-1, 0.846-1.151 mg·g^-1, respectively.

This simple accurate reproducible method can be used for the quality control and evaluate of compound Shuanghua tablets.

To establish a suitable method to determine the structure and source of impurities of colistimethate sodium (CMS) for drug quality control studies.

Frist-dimensional system: using Acquity UPLC^® Peptide CSH C₁₈(150 mm×2.1 mm, 1.7 μm) column, the mobile phase A was phosphate buffer (7.8 g·L^-1 sodium dihydrogen phosphate, adjusted to pH 6.4 with 1 mol·L^-1 sodium hydroxide)- acetonitrile (19∶1), the mobile phase B was phosphate buffer-acetonitrile (1∶1). Gradient elution was performed at a flow rate of 0.3 mL·min^-1. The column temperature was 30 ℃. Second-dimensional system: the Acquity BEH C₁₈ column (50 mm×2.1 mm, 1.7 μm) column was used with ammonium formate(A)-acetonitrile mixture as mobile phase with gradient elution. The flow rate was 0.2 mL·min^-1. The column temperature was 40 ℃. The detection wave length was 210 nm. The ESI source was used in negative ion mode.

The 2D-LC-Q TOF MS method was used to infer the structure of the 55 impurities in CMS, and the main sources were polymyxin E1-I, polymyxin E1-7MOA, polymyxin E3 and polymyxin E6.

The structure and source of impurities in CMS are determined by 2D-LC-Q TOF MS, and the changes in the content of impurities such as manufacturers and production processes are evaluated, which is conducive to improving the production process and controlling drug quality at the source.

To study and analyze rapid evaporative ionization mass spectrometry (REIMS) fingerprints of samples of Fritillariae Thunbergii Bulbus and Fritillariae Hupehensis Bulbus in different forms for authenticity discrimination with machine learning.

Aerosol formations from the samples by high temperature of dry burning method were ionized and determined by REIMS with m/z 50-1 200 as scanning range in sensitive mode and positive ion mode. The scanning time was 0.2 s and data was recorded as continuous mode. Then the basic situation of REIMS data distribution was studied and analyzed through the methods of cluster analysis, correlation analysis, similarity analysis and principal component analysis. And then logistic regression model with ridge regression (l2) as penalty parameter and quasi-Newton method (lbfgs) as optimization algorithm was established.

The REIMS fingerprints of the samples showed the characteristics of variety differences. Both cross validation and test set validation had an accuracy of 1.0, and the logistic regression model could accurately predict and distinguish the varieties of the samples.

The application prospect of REIMS technique combined with machine learning in the field of traditional Chinese medicine is very broad.

To explore the prepararation methods and rules of hair quality control samples which contained ketamine, norketamine or fluoroketamine, and the effects of different preparation and storage conditions on the performance of hair quality control samples.

Different preparation conditions were compared, such as different types of soaking solutions, solutions with different target contents, different amount of blank hair etc. The performances of hair quality control samples which were prepared in different conditions were systematically analyzed, and eighteen kinds of hair quality control samples with different contents of targets and different forms were prepared according to the rules, ACN-DMSO (1∶1, v/v, added 0.02 mol·L^-1 hydrochloric acid) was used to soak blank hair in different time periods to prepare hair quality control samples with a wide coverage. HPLC-MS/MS instruments and BEH C₁₈(100 mm×2.1 mm, 1.7 μm) column were used to test the content of targets in hair. Column temperature was 40 ℃, the mobile phases were aqueous solution with 0.1%(v/v) formic acid (A)-acetonitrile aqueous solution with 0.1%(v/v) formic acid (B), gradient elution (0-9 min, 5% B→100% B; 9-11 min, 100% B; 11-11.1 min, 100% B→5% B; 11.1-13 min, 5% B, a flow rats of 0.4 mL·min^-1, inject volume of 1 μL. The homogeneity, short term and long term stability in different storage conditions (temperature, humidity, light conditions, etc.) were also investigated.

The influences of different preparation conditions on the hair quality control samples were determined, soaking solutions had strong influences on the hair quality control samples, however the amount of blank hair had nearly no effects. All the samples prepared were uniform, F of each sample was lower than F_0.05(table) (3.02) according to the F-test method, and all the samples were stable, during storage at room temperature, refrigerated or frozen conditions for 6 months, the contents of the target substances in each sample were monitored, all of RSDs were <12%, and the t values of each sample were < t_{(0.05)(table)} (2.131 8) according to the T-test method.

This study provides preparation rules of hair quality control samples and also provides detailed reference data for subsequent preparation and storage of related hair quality control samples.

To establish a method for the detection of genetic impurity chloropropanol in hydroxypropyl distarch phosphate (HPDSP).

The method was performed with Agilent VF-WAX capillary column and temperature programmed by GC-MS. The initial temperature was 80 ℃ for 8 min, then increased to 220 ℃ at the rate of 35 ℃·min^-1 and maintained for 5 min with the flow rate of 2 mL·min^-1. The temperature of inlet was 200 ℃, and the injection volume was 1 μL without split. The detector was electron impact (EI) with selected ion monitoring (SIM) mode and ion source temperature at 230 ℃. The m/z of qualitative ions of 1-chloro-2-propanol were 45, 43, 79, 81, and the m/z of quantitative ion was 79. The m/z of qualitative ions of 2-chloro-1-propanol were m/z 58, 62, 63, 64, 65, and m/z of the quantitative ion was 62.

Good linear was achieved in the range of 20.04 ng·mL^-1 to 1 002 ng·mL^-1 (r=0.999 8, n=7) and the recovery rate ranged from 93.7% to 117.1% for 1-chloro-2-propanol. The contents of chloropropanol in 9 batches were within the range of 0.000 006%-0.000 08%.

The method shows the advantages of high sensitivity, good accuracy, linearity and can be used for the detection of genetic impurities in HPDSP.

To prepare and investigate the content determination of Nocardia rubra cell wall skeleton (N-CWS) loading film.

Taking chitosan and polyvinyl alcohol as film-forming materials, N-CWS film was prepared by solution casting method. The film was characterized by scanning electron microscopy(SEM), Fourier transform infrared spectroscopy(FTIR) and universal tensile testing machine. Determination of arabinose in N-CWS film was carried out by HPLC. The Kromasil C₁₈ column(150 mm×4.6 mm, 5 μm) was adopted, with the elution of 50 mmol·L^-1 phosphate buffer (pH 7.0)-acetonitrile (80∶20, v/v). The flow rate was 1.0 mL·min^-1, the detection wavelength was 254 nm, and the column temperature was 40 ℃.

When the mass ratio of chitosan to polyvinyl alcohol was 3∶2 and the mass ratio of membrane material to glycerol was 1∶2, the tensile modulus reached 2.47 mPa and the tensile strain at break was 136.67%. Scanning electron microscopy showed that N-CWS was distributed asymmetrically on the bottom of the film. The linear relationship of D-arabinose in the prepared film was good in the range of 1.1-220 μg·mL^-1, and the average recovery rate was 99.5%. The determination results of three batchs N-CWS films showed that the contents of D-arabinose in the films were (0.988±0.041) mg·g^-1, (1.035±0.049) mg·g^-1, (1.088±0.046) mg·g^-1, respectively.

The preparation process of N-CWS loading film is simple and feasible, and the content determination method is accurate and fast. This study can provide reference for the development of new dosage forms of N-CWS.

To develop a high performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method for the determination of vildagliptin in human anticoagulant plasma with ethylenediamine tetra acetic acid and apply it to the study of pharmacokinetics.

¹³C-¹⁵N-vildagliptin was used as internal standard (IS). After extraction from human plasma by protein precipitation with acetonitrile, all components were separated by a Hypurity C₁₈ column (150 mm×2.1 mm, 5 μm), using a gradient elution procedure consisting of methanol and 5 mmol·L^-1 ammonium formate at a flow rate of 0.5 mL·min^-1, and the column temperature was 40 ℃. Injection volume was just 2 μL. Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 304.3→154.2 for vildagliptin and m/z 310.3→160.3 for internal standard. Specificity, standard curve, lower limit of quantification, precision, recovery, matrix effect and stability were examined. Then this method was used to determine the plasma concentration of veragliptin in healthy subjects.

The calibration curve of vildagliptin in human plasma was linear over the concentration range of 1.11 to 534.0 ng·mL^-1. The lower limit of quantitation was 1.11 ng·mL^-1. The intra-and inter-day precisions at four quality control levels were within 0.9%-8.5%, and the accuracy was within 99.8%-109.3%. The data of short-term stability at room temperature displayed that the accuracy percentage of LQC samples was 92.0% for 0.5 h exposure, 87.6% for 1 h exposure, 71.2% for 2 h exposure. These of LQC samples chilled on ice was 102.0% for 0.5 h exposure, 94.5% for 1 h exposure, 86.6% for 2 h exposure. These results showed a phenomenon that there was a possible degradation of vildagliptin in plasma. The results of extraction recovery and matrix effect and other stability met the requirements of biological sample analysis. The pharmacokinetic study results of 8 healthy subjects showed that t_1/2 was (1.49±0.37) h, t_max was (2.06±1.11) h, C_max was (290.94±100.36) ng·mL^-1, AUC_{0-24 h} was (1 343.46±186.89) ng·h·mL^-1, AUC_0-∞ was (1 351.31±188.79) ng·h·mL^-1.

This method is easy to operate, has high specificity, and sensitivity. It has been successfully applied to the pharmacokinetic study of 8 healthy subjects after oral administration of 50 mg vigagliptin tablets on an empty stomach. Therefore, it can be used as a reliable detection method for human pharmacokinetic research and therapeutic drug monitoring.

To establish an HPLC method for the determination of the related substances in telmisartan.

Waters Symmetry Shield RP8 (150 mm×4.6 mm, 3.5 μm) column was adopted. The mobile phase A was 0.1% phosphoric acid solution (pH was adjusted to 3.0 with triethylamine), and the mobile phase B was acetonitrile. The gradient elution was performed. The flow rate, column temperature and wavelength were 0.8 mL·min^-1, 25 ℃ and 230 nm, respectively.

The resolutions between the peaks of telmisartan and nine known impurities were greater than 1.5. The limits of quantitation of all impurities were less than 40 ng·mL^-1, and the limits of detection of all impurities were less than 10 ng·mL^-1. The standard curves of telmisartan and its impurities were linear within the range 30-600 ng·mL^-1, and the correlation coefficients were all greater than 0.999 5. The average recovery rates of impurities Ⅰ-Ⅸ were 93.8%, 99.8%, 97.5%, 99.2%, 99.8%, 98.3%, 98.4%, 99.2% and 99.7%, respectively, and the RSDs of 9 results were all less than 2.0%. Changing the flow rate, column temperature, wavelength, mobile phase ratio and pH did not affect the detection results of the related substances. The results of maximum single impurity were 0.02% in three batches of telmisartan, and the results of total impurities were less than 0.10%.

The method is highly specific, sensitive, precise and accurate, and can be used for the determination of related substances of telmisartan.