To establish an UPLC-MS method for the analysis of salidroside, methyloleoside, specnuezhenide, acteoside, oleuropein, and G13 in plasma, and the differences in pharmacokinetic profiles of five different concoctions of Ligustri Lucidi Fructus, wine Ligustri Lucidi Fructus, vinegar Ligustri Lucidi Fructus, salt Ligustri Lucidi Fructus and steamed Ligustri Lucidi Fructus in vivo of rats were investigated.

SPF-grade male SD rats were randomly divided into 6 groups, and were given 4.2 g·kg^-1 of aqueous extracts of different concoctions of Ligustri Lucidi Fructus by gavage (for the amount of raw drug), and the plasma samples were methanol-precipitated proteins with geniposide as the internal standard, and the plasma samples were used to determine salidroside, methyloleoside, specnuezhenide, acteoside, oleuropein, and G13 in the plasma of the rats in the different time points by using the negative-ion SIM mode of UPLC-MS/MS. Kinetica 5.1 software was used to calculate the pharmacokinetic parameters, and GraphPad Prism 8.4.0 software was used to analyze the data.

The mass concentrations of salidroside, methyloleoside, specnuezhenide, acteoside and oleuropein were in the range of 2.00-1 385 ng·mL^-1, and the mass concentration of G13 was in the range of 1.30-650 ng·mL^-1, with good linearity, the relative standard deviations of the precision were all less than 10%, the recoveries of the extracts were all in the range of 85%-105%, and the matrix effect and stability were in accordance with the requirements of biological samples. The results of pharmacokinetic study showed that the AUC_0-∞, MRT_0-t, t_1/2, and C_max of acteoside were significantly higher in wine Ligustri Lucidi Fructus (P<0.01) compared to raw Ligustri Lucidi Fructus, which was 751.36 ng·mL^-1·h, 5.87 h, 377.82 h, and 38.11 ng·mL^-1, respectively. C_max, AUC_0-∞, and t_1/2 were significantly higher (P<0.01) for specnuezhenide and G13 in salt Ligustri Lucidi Fructus compared to raw Ligustri Lucidi Fructus, with C_max of specnuezhenide and G13 in salt Ligustri Lucidi Fructus were 66.45 ng·mL^-1 and 204.27 ng·mL^-1, respectively. The AUC_0-∞ were 342.69 ng·mL^-1 and 423.44 ng·mL^-1·h, and t_1/2 were 101.64 h and 15.98 h, respectively. Compared to raw Ligustri Lucidi Fructus, the C_max of oleuropein was significantly higher (P<0.05) in vinegar Ligustri Lucidi Fructus, wine Ligustri Lucidi Fructus, and steamed Ligustri Lucidi Fructus with 66.81 ng·mL^-1, 68.00 ng·mL^-1, and 66.38 ng·mL^-1, respectively. The AUC_0-∞ of salidroside and methyloleoside was the highest in vinegar Ligustri Lucidi Fructus, which was 5 782.74 ng·mL^-1 and 545.26 ng·mL^-1·h, respectively.

This study reveals the changing law of the six active ingredients in different artillery products of Ligustri Lucidi Fructus in vivo and their different characteristics, which provides a basis for the clinical application of different artillery products of Ligustri Lucidi Fructus.

To investigate the metabolites and metabolic pathways of WJ-14, a novel anti-depressant compound, in rats and human liver microsomes by HPLC-MS/MS.

Samples of rat plasma and urine, as well as in vitro incubation system of human liver microsomes were analyzed by HPLC-MS/MS. Chromatographic conditions: the chromatographic conditions were as follows: Hypersil BDS C₁₈ (100 mm×4.6 mm, 3 μm) column, with 0.1% formic acid aqueous solution (A)-methanol (B) as the mobile phase, gradient elution flow rate 0.4 mL·min^-1, column temperature 40 ℃, and injection volume 5 μL. The identification of metabolites and speculation on the metabolic pathways of WJ-14 were conducted by comparing the fragmentation mode and characteristic fragment ions of WJ-14.

A total of 12 metabolites of WJ-14 were identified, including 6 in rat and 6 in human liver microsomes, with two metabolites were detected in both rat and human liver microsomes. The major metabolic pathways of WJ-14 were identified as hydroxylation, demethylation, hydration, glucuronidation and methylation.

In this work, we investigated the metabolites and metabolic pathways of WJ-14 using HPLC-MS/MS for the first time. The metabolism of WJ-14 occurred in phase Ⅰ and phase Ⅱ metabolic reactions, in which hydroxylation in phase Ⅰ is dominant. The results of the current study may provide valuable information for the formulation development and application of WJ-14.

To develop a rapid, specific and sensitive UPLC-MS/MS method for the determination of vonoprazan in human plasma and its application in a bioequivalence study of two types of tablets.

A single dose, two-cycle, two products, and self-cross controlled trial design on bioequivalence was used. Plasma samples were collected from healthy human volunteers at different time points after oral administration with the test or reference product of 20 mg fumarate vonoprazan tablets under both fasting and fed conditions, respectively. The plasma samples were treated by acetonitrile protein precipitation and then analyzed by UPLC-MS/MS. Chromatographic separation of vonoprazan was achieved using a Waters ACQUITY UPLC® BEH C₁₈（50 mm × 2.1 mm, 1.7 μm）column at 40 ℃. The mobile phase consisted of water (containing 0.1% formic acid) for eluent A and acetonitrile (containing 0.1% formic acid) for eluent B under a gradient elution. An electrospray ionization (ESI) with multiple reaction monitoring (MRM) mode was used to monitor the precursor-product ion transitions of m/z 346.1→315.4 for vonoprazan and m/z 350.1→316.2 for vonoprazan-d₄.

The rang of linearity was 0.30-50.00 ng·mL^-1（r>0.998 9）, and the LLOQ was 0.30 ng·mL^-1. Intra- and inter-day precision values were within 5.7%, and intra- and inter-day accuracy values were ranged from -2.15% to 0.82%. Recovery, specificity, matrix effect and stability met the guiding principles. This method has been successfully applied to study the bioequivalence of vonoprazan fumarate tablets. The C_max of the test product in postprandial and fasting tests were (29.08±11.59) ng·mL^-1 and (26.87±8.14) ng·mL^-1, respectively, and the AUC_0-t was (258.90±87.71) h·ng·mL^-1 and (223.08±43.27) h·ng·mL^-1, respectively. The C_max of the reference product in postprandial and fasting tests were (28.73±10.25) ng·mL^-1 and (26.93±8.09) ng·mL^-1, respectively, and the AUC_0-t was (250.33±73.13) h·ng·mL^-1 and (227.56±46.26) h·ng·mL^-1, respectively. In the postprandial trial, the 90% CIs for the geometric mean ratios of C_max, AUC_0-t and AUC_0-∞ of the test and reference products were 88.64%-112.28%, 96.1%-108.2% and 96.6%-108.7%, respectively. And in the fasting trail, the 90% CIs for the geometric mean ratios of C_max, AUC_0-t and AUC_0-∞ of the test and reference products were 94.01%-106.23%, 94.71%-102.03% and 95.18%-102.47%, respectively.

This validated method has the advantages of simplicity, rapid, and high sensitivity. Test vonoprazan fumarate tablets are bioequivalent to the reference product.

To evaluate the differences of aqueous extract protein content and kinds among Hudilong origins in order to provide reference for the identification and quality evaluation.

The protein content of aqueous extract was determined, and the differences among the origins were compared by nonparametric tests. The protein fingerprints were established by SDS-PAGE, and the band matrix was constructed based on the molecular weight of the bands. The differences of the protein kinds among the 3 origins were compared and analyzed by CA and OPLS-DA.

There was no statistically significant difference in the aqueous extract protein content between the P. vulgaris and P. guillelmi, but both of them differed significantly from that of P. pectinifera (P<0.01). Aqueous extract protein content. from P. pectinifera was higher than from P. vulgaris or P. guillelmi. The results of SDS-PAGE showed that there were differences in the molecular masses and quantities of the protein bands of the 3 origins with relative molecular masses ranging from 10×10³ to 250×10³. The results of the CA and OPLS-DA showed that each of the origin of Hudilong could be differentiated. The differences of the protein relative molecular masses were 133.7×10³, 10.4×10³, 66.9×10³, 51.9×10³, 13.4×10³, 7×10³, 29.4×10³, 14.6×10³, 62.2×10³, 81.1×10³, 89.2×10³, 7.7×10³, and 101.7×10³, respectively.

There are differences in the aqueous extract protein among 3 origins of Hudilong. The P. vulgaris and P. guillelmi have high similarity in the aqueous extract protein components content and kinds. SDS-PAGE technique could be used to provide reference for the identification and quality evaluation.

To analyze the fragmentation rule and pathway of pelargonidin, cyanidin, delphinidin, peonidin, petunidin and malvinidol under UHPLC-QTOF-MS positive mode electric spray, identify the characteristic product ions of six anthocyanins, and provide a theoretical basis for the establishment of mass spectrometry database and detection methods.

The chromatographic conditions were as follows: chromatographic column, Fusion-RPC₁₈ (50 mm×2.0 mm, 4 μm), mobile phase 0.1% formic acid aqueous solution (A) and methanol (B), gradient elution (0-1 min, 95%A; 1-5 min, 95%A→10%A; 5-6 min, 1%A; 6-7 min, 95%A), flow rate 0.3 mL·min^-1, column temperature 40 ℃, and injection volume 10 μL. The mass spectrometry conditions were as follows: TOF MS-IDA MS/MS, curtain gas, 0.20 MPa, collision gas CAD 7 MPa, IS voltage, 5 500 V/-4500 V, ion source temperature, 500 ℃, nebulizer gas, GAS1, 0.38 MPa, auxiliary, GAS2, 0.48 MPa, DP voltage, ±60 V, fragmentation voltage, (35±15) V, and time 0.2 s. Under the condition of positive mode of electrospray, the mass spectrometry data of six anthocyanins were measured. According to the pyrylium ions formed by the 2-phenylchromogenic structure of anthocyanins, and combined with the auxiliary analysis of the mass spectrometer database, the possible product ions were deduced.

The results showed that the six anthocyanins mainly undergo cleavage reactions on the pyranium ring, ultimately generating intermediate ions of pyrogallol and benzyl alcohol. On the other way, it occured α cracking, σ cracking causes the loss of functional groups on the ring, ultimately resulting in the formation of Chain hydrocarbons without functional groups.

The research results can provide support for the mass spectrometry characteristic ion data of six anthocyanins, which can be used to establish ion library data for anthocyanin products and also provide reference for the development and research of detection methods.

To investigate different batches of Runbi Tongqiao drops by fingerprint and multi-index component content determination method, and to provide basis for its quality evaluation.

Acclaim TM-C₁₈ chromatographic column(250 mm×4.6 mm, 5 μm) was used with methanol(A)-acetonitrile(B) -0.2% formic acid aqueous solution(C) as the mobile phase with gradient elution. The flow rate was 0.8-1.0 mL·min^-1. The injection volume was 10 μL and the detection wavelength was 327 nm. The HPLC fingerprint of Runbi Tongqiao drops was established, and the quality consistency of Runbi Tongqiao drops was compared by stoichiometric method. The contents of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, luteoloside and isochlorogenic acid C were determined by HPLC.

A total of 14 common peaks were calibrated in the fingerprints of 10 batches of samples, and the similarities were ≥0.933. Seven common peaks of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, luteoloside and isochlorogenic acid C were identified by reference substances. The contents of seven components in Runbi Tongqiao drops were determined simultaneously, which were 0.131 5-0.133 8 mg·mL^-1, 0.095 5-0.098 9 mg·mL^-1, 0.087 4-0.090 1 mg·mL^-1, 0.012 8-0.015 8 mg·mL^-1, 0.010 3-0.013 7 mg·mL^-1, 0.022 7-0.024 9 mg·mL^-1 and 0.006 8-0.008 6 mg·mL^-1, respectively.

The established fingerprint of Runbi Tongqiao drops is stable and reliable, and the simultaneous determination method of multi-component content is simple and fast. It can be used for the quality control of Runbi Tongqiao drops, which lays a solid foundation for the follow-up study of Runbi Tongqiao drops.

To identify the risks and provide a scientific basis for the formulation of the limit standards by the determination and risk assessment of pesticide residues in Yixintong tablets and hawthorn leaf extracts.

The samples were extracted with acetonitrile by high speed homogenater, and purified by solid - phase extraction(SPE) column of envi-carb/NH₂. 262 pesticides in hawthorn leaf extracts and Yixintong tablets were detected by GC-MS/MS and LC-MS/MS. Moreover, the acute and chronic intake risks were calculated using the deterministic risk assessment model.

25 and 31 types of pesticides were detected in hawthorn leaf extracts and Yixintong tablets, respectively. 18 types of pesticides were detected in all of them. The contents were 0.004-1.457 mg·kg^-1, 0.007-2.1 mg·kg^-1, respectively. The results of risk assessment revealed that the short-term hazard index(HIa) of hexaconazole was 1 and the risk was needed to be paid more attention. HIa and long-term hazard index(HIc) of other pesticides detected in Yixintong tablets and hawthorn leaf extracts were much lower than 1, indicating an acceptable risk.

In the present study, the pesticide residues were explored, and their health risks were assessed；therefore our study provided technical support for the improvement of risk assessment applicable to traditional Chinese medicines (TCMs) and the formulation of relevant pesticide residue limit standards.

To study the related substances in salbutamol sulfate inhalation aerosol during national drug sampling and testing, and to compare the impurity content and evaluate the quality between samples from various enterprises.

HPLC external standard method was utilized to simultaneously determine the content of related substances A, B, C, D, E, F, G, H, I, J, N, and other unknown impurities in salbutamol sulfate inhalation aerosol. Thermo Synchronis C₈ chromatography column (250 mm×4.6 mm, 5 μm) was used. Sodium heptane sulfonate solution-acetonitrile was used as the mobile phase. Linear gradient elution was performed and the flow rate was 1.0 mL·min^-1. Column temperature was 40 ℃ and detection wavelength was 220 nm. Injection volume was 20 μL. The sources of impurities through forced degradation experiments were explored. Toxicity prediction software for impurity toxicity assessment was applied.

After method validation, the specificity of the method was good, and the separation degree between each impurity peak was greater than 1.5. RSDs of precision test were 0.30%-1.7%(n=6)；mass concentrations of linear range were from 0.050 to 5.000 μg·mL^-1(r=0.999 9). Limit of quantitative was in the range of 0.025-0.200 μg·mL^-1, limit of detection was in the range of 0.008-0.070 μg·mL^-1. The repeatability RSD of raw materials was 0.80%-3.8%, and the recovery rate was 95.2%-104.8%. The repeatability RSD of inhaled aerosol was 1.2%-2.9%, and the recovery rate was 98.7%-102.8%. The forced degradation test showed that impurities D, F, I, J, and N were all degradation impurities. 110 batches of samples were checked and the results of the relevant substances met the regulations. In the samples of diverse enterprises, impurities C, D, F, and N were detected more frequently, while impurities E, G, and H were not detected. Impurity J was only detected in one batch. The predicted impurity D by QSAR software falls to ICH M7 (R2) level 2.

The established method is sensitive and accurate, and can accurately quantify the content of related substances in salbutamol sulfate aerosol, providing effective technical support for systematic supervision. Further toxicity studies should be conducted on impurity D and reasonable limits should be established.

To establish an HPLC method for determination of related substances in apixaban API.

The analytical column was an ACE Excel3 C₁₈-PFP (150 mm×4.6 mm, 3 μm）. The mobile phase A was buffer(30 mmol·L^-1 ammonium acetate in water)-acetonitrile（90∶10） and the mobile phase B was buffer(30 mmol·L^-1 ammonium acetate in water)-acetonitrile（5∶95）. The whole run carried out by gradient elution at a flow rate of 1.2 mL·min^-1. The detection wavelength was set at 280 nm, the column temperature was 40 ℃ and the injection volume was 10 μL.

Apixaban was separated completely from the impurities and degradation products(the resolution>2.0). The test solution was stable for at least 48 h. The LOQs of apixaban, methyl ester product, ethyl ester product, chlorine impurity, dehydrogenation impurity, bihydrolytic impurity, ringopen methyl ester product, cyclate, impurity D, hydrolytic impurity, ringopen acid impurity, ringopen amide impurity and 5-chlorhexyl chloride derived impurity, were all 0.05%. The linear correlation coefficients of apixaban, methyl ester product, ethyl ester product, hydrolytic impurity, ringopen acid impurity, ringopen amide impurity and 5-chlorhexyl chloride derived impurity were all more than 0.99. The range were from the LOQ for impurity content to 150% of the target concentration. The average recoveries（RSD）(n=9) of methyl ester product, ethyl ester product, hydrolytic impurity, ringopen acid impurity, ringopen amide impurity and 5-chlorhexyl chloride derived impurity were 102.0%（2.7%）, 106.4%（2.2%）, 111.2%（4.0%）, 104.4%（2.9%）, 102.9%（2.7%）, 101.8%（2.9%）. The repeatability and intermediate precision completely met the requirements. The impurities contents in three batches of apixaban API 6 months accelerate stability test completely met the requirements, respectively.

This method is simple, rapid, sensitive and specific to be used for the determination of related substances in apixaban API.

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

HPLC was adopted on a PFP column (250 mm×4.6 mm, 5 μm) with a gradient elution system of 20 mmol·L^-1 potassium dihydrogen phosphate solution and methanol, the flow rate was 1.0 mL·min^-1, and the column temperature was maintained at 30 ℃. The detection wavelength was set at 265 nm.

The resolutions were good between the peaks of nifedipine and ten known impurities, including impurity D, 2-nitrobenzaldehyde, monoamide, hydroxy dehydro lactone, impurity C, dehydro-N-oxide, impurity A, impurity B, m-nifedipine, p-nifedi-pine. The resolutions between the known impurity peaks were not less than 1.5, the resolutions between the main peak of nifedipine and it’s front and back impurity peaks were not less than 2.0. The calibration curves of mass concentration of above known impurities were linear respectively in their concentration range of 0.000 2-0.015 mg·mL^-1(r>0.999, n=7). The correlation coefficients of above known impurities were 1.000, 1.000, 1.000, 1.000, 0.999 9, 0.999 9, 0.999 9, 1.000, 0.999 9, 0.999 9, respectively. The average recovery rates of above known impurities were 93.1%(RSD=2.3%), 110.6%(RSD=1.9%), 109.2%(RSD=2.0%), 111.0%(RSD=2.1%), 108.1%(RSD=1.9%), 112.4%(RSD=1.8%), 110.8%(RSD=1.9%), 91.5%(RSD=3.1%), 98.9%(RSD=2.7%), 110.1%(RSD=2.6%), respectively. The detection limit of above known impurities was 0.000 06 mg·mL^-1, the quantification limit of above known impurities was 0.000 2 mg·mL^-1. The impurity determination results of the three batches of nifedipine samples showed that the content of the known impurities and the maximum single unknown impurity were less than 0.1%, the total impurities contents were less than 0.5%.

The method has good sensitivity and specificity, and it is suitable for the quality control of nifedipine.

To establish an HPLC-CAD method for the determination of related substances in peramivir injection and to analyze the impurity profile.

Welch Ultimate Polar RP column (250 mm×4.6 mm, 3.5 μm) was used with 5 mmol·L^-1 ammonium formate solution (pH adjusted to 4.6 with formic acid) -acetonitrile (95∶5) as mobile phase A and mobile phase A-acetonitrile (50∶50) as mobile phase B under gradient elution at the flow rate of 0.8 mL·min^-1. Column temperature was 30 ℃. CAD atomizer temperature was 50 ℃, acquisition frequency was 5 Hz and filter was 3.6 s. The degradation pathway and impurity structure of peramivir were estimated by LC-MS/MS.

The separation between peramivir and the impurities was good. The mass concentration of peramivir and 7 impurities showed good linear relationships with the peak area in the ranges of 0.2-12 μg·mL^-1. The limits of quantitation were 4.32-12.8 ng, and the limits of detection were 2.16-6.44 ng. The average recovery (n=9) of impurity Ⅲ was 96.2%, RSD was 1.8%. The control solution and the test product solution were stable for 102 hours at room temperature. After fine-tuning the parameters of liquid chromatography, there was no influence on the detection results of related substances. Based on LC-MS/MS, the structure and possible degradation pathway of the degraded related substances were deduced.

This method is accurate, reliable and specific for the determination of related substances in peramivir injection, and provides a basis for the establishment of quality standards for this variety.

To determine the contents of 28 elements in Xianzhuli under processes of dry distillation and fire preparation by inductively coupled plasma mass spectrometry (ICP-MS), and evaluate the rationality of the current temperature used in the dry distillation process as well as whether the preparation process of commercial samples conforms to the traditional or modern one.

The samples of Xianzhuli were pre-treated with nitric acid before microwave digestion. The contents of 28 elements in 59 batches of Xianzhuli samples were determined by inductively coupled plasma mass spectrometry(ICP-MS), and the methodology was investigated.

The standard curve of 28 elements had a good linear relationship with r≥0.999 2. The detection limits were 0.007 1-1.249 5 ng·mL^-1, the RSDs for precision, repeatability and repeatability tests were 0.30%-3.5%, 0.69%-6.4% and 1.1%-3.3%, respectively and the recovery rates were 88.6%-105.5% with RSDs ranged from 1.0% to 3.2%. The contents of Na, Mg, K, Ca, Mn, Fe, Zn and Rb in 59 batches of Xianzhuli were high, and the contents of heavy metal elements did not exceed the limit requirements. The results of cluster analysis showed that the samples prepared by dry distillation and fire preparation were clustered into one class. By principal component analysis, 7 principal components were obtained, and the cumulative variance rate was 75.6%. Mg, K, Ca, Cr, Fe, Co, Cu, Rb, Cd, Ba, Tl and Pb were identified as the characteristic elements of Xianzhuli.

Based on the contents of beneficial and harmful elements, it is found that the contents of toxic and harmful elements in the sample processed with 160 ℃ dry distillation are lower than processed with fire preparation. And the contents of beneficial elements are similar in two kinds of samples. This temperature is consistent with the dry distillation process temperature approved by provincial drug regulatory authorities for currently certified enterprises. Most of the commercially available samples meet the requirements of traditional or modern processes, and a few may have quality differences due to different processes. The determination and analysis of heavy metals and other elements in Xianzhuli under different processes can provided scientific basis for safe production and rational use of Xianzhuli.

To establish the HPLC fingerprint and multi-component quantitative analysis of Hanchuang Zupa granules, and evaluate the quality of multiple batches of Hanchuang Zupa granules by chemical pattern recognition technology.

The sample pretreatment conditions and chromatographic analysis conditions of Hanchuang Zupa granules were optimized, and the optimal HPLC fingerprint and multi-component quantitative analysis method were established as follows: stationary phase was YMC-Pack ODS-A column (250 mm×4.6 mm, 5 μm, 12 nm) was adopted, and the mobile phase was acetonitrile-water (containing 0.1% phosphoric acid) with gradient elution, the detection wavelength was 220 nm, the column temperature was 30 ℃, the flow rate was 1.0 mL·min^-1. Hierarchical cluster analysis (HCA), principal components analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied to evaluate the quality of 17 batches of Hanchuang Zupa granules.

Methodological investigation of HPLC fingerprint and content determination were well verified and met the analysis requirements. A total of 25 common peaks were obtained by full peak matching, and eight of them were identified by comparing with the retention time of mixed reference substances. The similarities of 17 batches of samples were above 0.90, which showed good consistency and stability between the samples. Seventeen samples could be classified into three clusters. Three principal components from 21 common peaks were extracted by PCA. Six quality differential compounds were presented in the fingerprints by OPLS-DA, including rutoside, gallic acid, ammonium glycyrrhizinate, chlorogenic acid and so on. The resolution and linear relationship of eight components in quantitative analysis were good. The average recovery rates were 98.0%-99.1% with RSD≤2.0%.

In this study, the qualitative analysis of HPLC fingerprint and quantitative analysis of multiple index components is specific, simple and accurate, which can provide a reference for the quality control and quality evaluation of Hanchuang Zupa granules.

To identify the authenticity of the Longgu, and reveal the scientific illustration for superior quality of white Longgu.

In this study, the quality of 88 batches of Longgu was evaluated by cluster analysis, principal component analysis and correlation analysis based on character, ultraviolet fluorescence and results obtained with inductively coupled plasma mass spectrometry, color analyzer and nuclear radiation detector.

The Longgu spots on the surface of Longgu were the key identification points of genuine Longgu, and the Longgu spots were mainly composed of Mn elements. Bright blue fluorescence could be seen in the fresh section of keel under 365 nm. Among the 42 elements determined, only Mg and Zn were higher in the fake Longgu than in the genuine Longgu. Other elements were lower in the fake Longgu than in the genuine Longgu. Heavy metals and harmful elements in counterfeit samples were below limits in pharmacopoeia, and cluster analysis showed that all counterfeit samples were grouped into one group separately. The Longgu could be divided into four color types: white, cyan, yellow and brown. The larger a * was, the redder the color of Longgu was, the higher the contents of Fe and harmful elements (As, Cu, Pb and Cd) were. And the contents of element V were strongly correlated with those of As, Cu, Pb and U, which could be used as index element of heavy metals and harmful elements. The contents of radioactive element U and the radiation values were highest in brown Longgu, second highest in yellow Longgu was the, lower in cyan Longgu, and lowest in white Longgu. The average content of U in brown Longgu was 0.021% with the highest content of 0.09%, and the average radiation value was 0.33 μSv·h^-1 (Background value was 0.18 μSv·h^-1) with the highest value of 0.47 μSv·h^-1. The average content of U in yellow Longgu was 0.012% with the highest content of 0.021%, and the average radiation value was 0.32 μSv·h^-1 with the highest value of 0.39 μSv·h^-1. The average content of U in cyan Longgu was 0.008 9% with the highest content of 0.012%, and the average radiation value was 0.30 μSv·h^-1 with the highest value of 0.35 μSv·h^-1. The average content of U in white Longgu was 0.006 7% with the highest content of 0.009 1%, and the average radiation value was 0.28 μSv·h^-1 with the highest value of 0.32 μSv·h^-1.

Considering the harmful elements and radiation safety, the white Longgu has better quality, and the brown Longgu has worse quality.

To establish a quantitative analysis of multi-components by single marker (QAMS) method to simultaneously determine the contents of kalangin, diphenylheptane A, galangin, kaempferin and galangin-3-O-methyl ether.

Hypersil ODS2 C₁₈ (250 mm×4.6 mm, 5 μm) was used by high performance liquid chromatography (HPLC) and was eluted with 0.3% acetic acid in water (A) and acetonitrile (B) (0-2 min, 10%B→15%B；2-5 min, 15%B→20%B；5-20 min, 20%B→35%B；20-30 min, 35%B→40%B；30-55 min, 40%B；55-60 min, 40%B→100%B), the column temperature was 30 ℃, the volume flow rate was 0.8 mL·min^-1, and the detection wavelength was 254 nm. The relative correction factors of each chemical component were calculated with gingerin as the internal reference, and the content was determined, which was compared with the results of the external standard method, and the quality of galangal from different origins was evaluated by chemical pattern recognition.

Kaempferol, diphenylheptane A, galangin, kaempferin and galangin-3-O-methyl ether had a good linear relationship in the ranges of 0.005 5-0.110 0, 0.140 0-2.800 0, 0.149 6-2.992 0, 0.021 5-0.430 0 and 0.022 2-0.444 0 μg, respectively, and the average sample recoveries were 100.7%, 101.4%, 99.9%, 100.9% and 101.7%, respectively. The RSDs were 1.3%, 2.8%, 0.83%, 1.4% and 1.8%, respectively. Quantitative analysis of multicomponents by single marker method and external standard method was no significant difference in the results.

This method is rapid, accurate and specific, which can provide a reference for the quality control of galangal.

To establish a method for the simultaneous determination of six components (rutin, naringin, neohesperidin, quercetin, purpurin and mollugin) in Huazhi tablets and Huazhi capsules by HPLC.

The assay was performed on an Agilent ZORBAX SB-Aq (150 mm×4.6 mm, 5 μm) and the sample was eluted by mobile phase consisting of acetonitrile(A) -0.1% phosphoric acid(B) with a gradient at a flow rate of 1.0 mL·min^-1 and the column temperature was 30 ℃. The detection wavelengths were set at 250 nm for rutin during 0-20 min, 283 nm for naringin and neohesperidin during 20-37 min, and 250 nm for quercetin, purpurin and mollugin during 37-60 min.

Rutin, naringin, neohesperidin, quercetin, purpurin and mollugin exhibited good linearity(r>0.999 0) in the ranges of 37.26-1 863.20 μg·mL^-1, 11.27-563.70 μg·mL^-1, 9.58-479.04 μg·mL^-1, 1.92-95.90 μg·mL^-1, 0.52-25.83 μg·mL^-1 and 0.90-45.10 μg·mL^-1, respectively. The average recoveries of the above mentioned six components in Huazhi tablets (n=6) were 103.2%(RSD=1.4%), 99.5%(RSD=1.7%), 97.7%(RSD=1.2%), 95.2%(RSD=1.1%), 104.2% (RSD=1.2%) and 104.2%(RSD=0.80%), respectively, and the average recoveries of the above mentioned six components in Huazhi capsules (n=6) were 102.5% (RSD=1.3%), 96.9%(RSD=0.48%), 97.1%(RSD=1.1%), 96.9%(RSD=0.78%), 102.3%(RSD=1.4%) and 101.8%(RSD=1.2%), respectively. The content ranges (mean ± SD) of rutin, naringin, neohesperidin, quercetin, purpurin and mollugin in the 17 batches of Huazhi tablets and Huazhi capsules were 31.14-98.25(44.33±15.65) mg·g^-1, 5.12-20.85(12.96±5.85) mg·g^-1, 4.03-17.00(10.14±5.17) mg·g^-1, 0.63-7.17(1.97±1.49) mg·g^-1, 0.23-1.32(0.57±0.28) mg·g^-1 and 0.67-1.72(1.08±0.29) mg·g^-1, respectively.

The established method can simultaneously determine six components in Huazhi tablets and Huazhi capsules and can provide a reference for the quality control of Huazhi tablets and Huazhi capsules.

To establish a quality evaluation method of Erdi Xiaoke mixture based on HPLC fingerprint, multi-component determination and chemometric analysis.

The separation was performed on a 30 ℃ thermostatic Acutfex PW-C₁₈ (250 mm×4.6 mm, 5 μm) column, with the mobile phase comprising of acetonitrile -0.1% phosphoric acid flowing at 1.0 mL·min^-1 in a gradient elution manner, and the detection wavelength was set at 285 nm to establish HPLC fingerprint of Erdi Xiaoke mixture. Contents of 11 components [5-hydroxymethyl furfural(5-HMF), salvianic acid A, chlorogenic acid, caffeic acid, calycosin-7-glucoside, acteoside, isochlorogenic acid B, isochlorogenic acid C, rosmarinic acid, salvianolic acid B and formononetin] in 12 batches of Erdi Xiaoke mixture were determined, and similarity evaluation, cluster analysis, principal component analysis and orthogonal partial least squares discriminant analysis were used to comprehensively evaluate the quality of Erdi Xiaoke mixture.

The 11 constituents showed good linear relationships within their respective ranges(r≥0.999 6), with average recovery rates of 95.3%-101.5%, and the RSDs were in the range of 1.1%-2.3%. There were 18 common peaks in the fingerprints for 12 batches of samples with the similarities above 0.960. The range of the content of the above 11 components in the 12 batches of samples were as follows as 43.40-65.70, 219.43-274.70, 119.00-164.78, 11.87-18.17, 42.80-56.86, 10.01-20.71, 8.21-14.73, 40.15-57.39, 43.29-60.29, 755.22-1 208.50, 2.47-4.44 μg·mL^-1. And 12 batches of Erdi Xiaoke mixture could be clustered into three categories with some differences in sample quality among different batches. In addition, 5-HMF, isochlorogenic acid B and chlorogenic acid were the main potential markers affecting the quality of Erdi Xiaoke mixture.

This method is stable, reliable, accurate and sensitive, and can be used to control and comprehensively evaluate the quality of Erdi Xiaoke mixture.

To develop a flow-through cell method for the dissolution test of omega-3-acid ethyl ester 90 soft capsules and compare the dissolution behaviors from different manufacturers.

The medium (surfactant and its concentration, pH, dosage of pepsin), flow rate and system mode (closed versus open) were investigated. The samples were collected at the specified time and determined by HPLC. The similarity of the dissolution curves between generic drugs and reference listed drug was evaluated by similarity factor (f₂).

A closed-loop mode of flow-through cell apparatus was employed, with 0.01 mol·L^-1 hydrochloric acid solution containing 4.0% Triton X-100 as the dissolution medium, and the flow rate was 2.0 mL·min^-1. The dissolution curves of the samples that have passed consistency evaluation are similar to those of the reference and the samples produced by enterprise in the declaration stage are partly similar. The method has effective distinguish ability for product quality and different prescriptions.

The newly established method can be used for the quality control of omega-3-acid ethyl ester 90 soft capsules, and can provide references for further consistency evaluation and the dissolution method development of lipid-filled soft gelatin capsule (SGC).