Determination and Mechanism Prediction of Potential Active Ingredients in Erdongtang Based on UHPLC-QqQ-MS and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo establish an ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry（UHPLC-QqQ-MS） for determination of the active ingredients in Erdongtang， and to predict the targets and pathways of anti-insulin resistance action of this formula. MethodThe analysis was performed on an ACQUITY UPLC BEH C18 column（2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution（A）-acetonitrile（B） for gradient elution（0-3 min， 90%-87%A； 3-6 min， 87%-86%A； 6-9 min， 86%-83%A； 9-11 min， 83%-75%A； 11-18 min， 75%-70%A； 18-19 min， 70%-52%A； 19-22 min， 52%A； 22-25 min， 52%-5%A； 25-27 min， 5%-90%A； 27-30 min， 90%A）. The contents of active ingredients in Erdongtang was detected by electrospray ionization（ESI） and multiple reaction monitoring（MRM） mode under positive and negative ion modes. On this basis， network pharmacology was applied to predict the targets and pathways of Erdongtang exerting anti-insulin resistance effect. ResultThe 20 active ingredients in Erdongtang showed good linear relationships within a certain mass concentration range， and the precision， stability， repeatability and recovery rate were good. The results of determination showed that the ingredients with high content in 15 batches of samples were baicalein（1 259.39-1 635.78 mg·L-1）， baicalin（1 078.37-1 411.52 mg·L-1）， the ingredients with medium content were mangiferin（148.59-217.04 mg·L-1）， timosaponin BⅡ（245.10-604.89 mg·L-1）， quercetin-3-O-glucuronide（89.30-423.26 mg·L-1）， rutin（46.91-1 553.61 mg·L-1）， glycyrrhizic acid（55.97-391.47 mg·L-1）， neomangiferin（37.45-127.03 mg·L-1）， nuciferine（0.89-63.48 mg·L-1）， hyperoside（6.96-136.78 mg·L-1）， liquiritin（30.89-122.78 mg·L-1）， liquiritigenin（26.64-110.67 mg·L-1）， protodioscin（58.57-284.26 mg·L-1）， the ingredients with low content were wogonin（7.16-20.74 mg·L-1）， pseudoprotodioscin（5.49-22.96 mg·L-1）， ginsenoside Rb1（7.31-23.87 mg·L-1）， ginsenoside Rg1（10.78-28.33 mg·L-1）， ginsenoside Re（7.78-24.76 mg·L-1）， ophiopogonin D（2.08-4.29 mg·L-1）， methylophiopogonanone A（0.74-1.67 mg·L-1）. The results of network pharmacology indicated that the mechanism of anti-insulin resistance exerted by Erdongtang might be related to the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway. ConclusionThe established UHPLC-QqQ-MS has the advantages of simple sample processing， strong exclusivity and high sensitivity， and can simultaneously determine the contents of the main ingredients from seven herbs in Erdongtang， which can lay the foundation for the development of Erdongtang compound preparations. The results of the network pharmacology can provide a reference for the mechanism study of Erdongtang in the treatment of type 2 diabetes mellitus.

Quantitative estimation of Carthamin and Carthamidin from the Florets C. tinctorius L., (Safflower Florets)

Natural colorants derived fom plant materials have gained increasing popularity due to their non toxic nature. pigment extraction from the florets is normally done by Soxhlet extraction, maceration, and hydro distillation are conventional methods that have been widely used in industry and laboratory .phytochemical analysis of safflower florets revealed the plant presence of high amount of Carthamin and carthamidin.

Estimation of Lipid and Fatty Acids Composition over the Ground Part of Nepeta olgae Regel (L.) Plants Growing in Namangan Region

The article is devoted to the study of lipids and fatty acid composition of the above-ground part of the Nepeta olgae Regel (L.) plant of the Laminaceae family. It was found that the content of neutral lipids (NL) is 5.54%, PL - 6.12%, and total lipids (NL, PL) - 11.66%. Of the neutral lipids, the unsaponifiable substances (HB) had a bright yellow color, which is explained by a small amount of carotenoids (88.87 mg%). Glycolipids dominate in PL. Among the unsaponifiable substances were found biologically active components such as hydrocarbons, carotenoids, aliphatic alcohols, sterols and triterpenols. Phytosterols were the main component of unsaponifiable NS. Quantitative and qualitative analysis of fatty acids from the plant Nepeta olgae Regel (L.) was carried out by gas chromatography (GC). 28 acids were identified, of which 11 compounds are saturated, and 7 compounds are unsaturated fatty acids. Of the fatty acids, the main ones are linolenic 18:3 (35.48), palmitic 16:0 (33.38%), as well as ?-3 polyunsaturated fatty acids, including eicosanoic 20:1, cis-11,14-eicosadienoic 20:2, 8,11,14-eicosatriene 20:3 + arachidonic 20:4. Extracts of Nepeta olgae Regel (L.) were distinguished by a high content of polyunsaturated acids, which determines their potential biological activity.

Comparative Analysis of the Elementary and Amino Acid Composition of Nepeta olgae Regel L. Plants Growing in Uzbekistan

This article for the first time presents the results of the study of qualitative and quantitative elemental and amino acid composition of the aboveground part of the plant Nepeta olgae Regel (L.) taken in the territory of Chust and Kosonsai districts (from the slopes of Gova and Kosonsai mountains) of Namangan region during the period before and during flowering (May-June, 2021-2022). The use of instrumental analysis of high-throughput energy dispersive X-ray fluorescence spectrometry, allowed to establish 20 mineral elements in the plant Nepeta olgae Regel (L.), among which to vital 9 elements and 3 to conditionally necessary. The amino acid composition of the plant Nepeta olgae Regel (L.) was studied by high performance liquid chromatography (HPLC) and 17 compounds were identified. Of these, 8 were substitutable and 9 essential amino acids.

Impact of Coronary Plaque on the Precision of Computational Fractional Flow Reserve Derived from CTA / 中山大学学报(医学科学版)

ObjectiveThe fractional flow reserve （FFR） computed from coronary computed tomographic （CT） angiograms makes it possible to noninvasively assess coronary artery disease， but the impact of plaque on FFR derived from computed tomography angiography （CTA） is still unknown. The study used invasive FFR as the reference standard to analyze the impact of plaque on coronary computed tomography angiography （CCTA）-based quantitative flow ratio （CT-QFR）. MethodsThe retrospective study included 108 patients with suspected coronary heart disease （CHD） who underwent both CCTA and FFR within 60 days. CCTA images were analyzed by the software. We obtained the CT-QFR of target vessels， perfomed the quantitative and qualitative analyses on target vascular plaques， including total plaque volume （TPV）， plaque burden， calcified plaque volume （CPV）， fibrous plaque volume （FPV）， lipid plaque volume （LPV）， and the presence or absence of high-risk plaque. ResultsAccording to the difference between CT-QFR and FFR at blood vessel level， 137 target vessels of 108 patients were divided into the overestimated group （difference＞0.03， n＝29）， reference group （-0.03≤difference≤0.03， n＝88） and underestimated group （difference＜-0.03， n＝20）. The underestimated group （14.81mm3） presented higher LPV than overestimated group （1.97mm3， P < 0.05）. There was a negative correlation between LPV and the difference （P＜0.05）. ConclusionsWhen CT-QFR is used to estimate hemodynamics of coronary artery stenosis， the presence of lipid plaque may underestimate the virtual FFR.

Content determination of 6 components in Jinlian qingre granules by QAMS method based on a variety of internal reference substances / 中国药房

OBJECTIVE To establish a quantitative analysis of multi-components by single marker （QAMS） method based on a variety of internal reference substances for the content determination of 6 components in Jinlian qingre granules， such as mangiferin， 2″-O-β-L-galactopyranosylorientin， orientin， veratric acid， vitexin， harpagoside. METHODS The determination was performed on Agilent Eclipse Plus C18 column with mobile phase consisted of acetonitrile-0.1% phosphoric acid solution （gradient elution） at the flow rate of 1 mL/min. The column temperature was 30 ℃， and the detection wavelength was set at 270 nm. Taking orientin， vitexin and 2″-O-β-L-galactopyranosylorientin as internal references， the relative correction factors （RCF） of the other 5 components to be determined and internal substances were determined by QAMS. The contents of 6 components in 21 batches of Jinlian qingre granules were calculated and then compared with the results of the external standard method. RESULTS The contents of mangiferin， 2″-O-β-L-galactopyranosylorientin， orientin， veratric acid， vitexin and harpagoside in 21 batches of samples were determined by QAMS in the range of 0.234-0.516， 1.804-2.270， 2.143-2.606， 0.190-0.223， 0.594-0.782， 0.080-0.152 mg/g； the contents of them determined by external standard method were 0.235-0.523， 1.798-2.265， 2.137-2.599， 0.190-0.224， 0.597-0.786， 0.077-0.151 mg/g， respectively. The percentage difference between the results measured by the two methods should not exceed 4.00%. CONCLUSIONS QAMS has been constructed for the simultaneous determination of 6 components in Jinlian qingre granules based on a variety of internal reference substances. The results obtained by this method are not significantly different from those obtained by the external standard method， and can be used for the quality control of Jinlian qingre granules.

AI Cytomorphology Combined with DNA-image Cytometry for Identifying Benign and Malignant Pleural Effusion and Ascites / 肿瘤防治研究

Objective To explore the diagnostic value of artificial intelligence (AI) cytology combined with DNA-image cytometry (DNA-ICM) auxiliary diagnostic system for the identification of benign and malignant pleural effusion and ascites. Methods Liquid-based cytology technology (LCT), DNA-ICM, AI, and AI combined with DNA-ICM were used to identify benign and malignant pleural effusion and ascites specimens in 360 cases, and their sensitivity, specificity, accuracy, Kappa value, Youden index and AUC were statistically analyzed. Results The sensitivity, specificity, and accuracy of AI combined with DNA-ICM in detecting benign and malignant pleural effusion and ascites were 95.23%, 94.12%, and 94.44%, respectively, which were higher than those of the three other separate detection methods (all P < 0.05). The kappa values of LCT, DNA-ICM, and AI were 0.646, 0.642, and 0.586; their Youden index values were 0.693, 0.687, and 0.676, and their AUC values were 0.846, 0.843, and 0.838, respectively. The Kappa value of AI combined with DNA-ICM was 0.869, the Youden index was 0.893, and AUC was 0.947, which were all higher than those of the three detection methods alone. Conclusion Among the three separate detection methods, LCT has the highest reliability, authenticity, and diagnostic value, and it can be used as a common method for the clinical identification of benign and malignant pleural effusion and ascites. The diagnostic performance of AI combined with DNA-ICM auxiliary diagnosis system in identifying benign and malignant pleural effusion and ascites is better than those of the three separate detection methods and can be used as a reliable method for the clinical identification of benign and malignant pleural effusion and ascites.

Comprehensive quality evaluation of Tangwei capsule based on HPLC-QAMS multi-index quantitative determination combined with chemometrics and EW-TOPSIS method / 浙江大学学报·医学版

OBJECTIVES@#To detect the contents of Tangwei capsule main components with high performance liquid chromatography-quantitative analysis of multicomponents by single marker (HPLC-QAMS) method and to evaluate the quality with chemometrics and entropy weight-technique for order preference by similarity to an ideal solution (EW-TOPSIS).@*METHODS@#A symmetry C18 column and 0.1% formic acid-acetonitrile as mobile phase were used for HPLC of Tangwei capsule. The contents of 3'-hydroxypuerarin, puerarin, 3'-methoxypuerarin, methylnissolin-3-O-glucoside, calycosin, formononetin, rosmarinic acid, salvianolic acid B, dihydrotanshinone Ⅰ, cryptotanshinone, tanshinone Ⅰ, tanshinone ⅡA and cucurbitacin B in 15 batches of Tangwei capsule were determined simultaneously. The quality differences of 15 batches of samples were analyzed by chemometrics and EW-TOPSIS.@*RESULTS@#The HPLC-UV showed that 13 components had good linear relationships in corresponding concentration ranges (r≥0.9991). The relative standard deviations (RSD) of precision, repeatability and stability were all less than 2.00%. The average recovery rates were between 96.86% and 100.13%, and RSD were all less than 2.00%. Cluster analysis showed that 15 batches of samples were clustered into 3 groups. Partial least squares-discriminant analysis showed that salvianolic acid B, formononetin, puerarin, 3'-methoxypuerarin and rosmarinic acid were the main potential markers affecting the quality of Tangwei capsule. EW-TOPSIS analysis showed that the quality of S12-S15 was superior.@*CONCLUSIONS@#The analytical method established in this study can be used for the comprehensive evaluation of the quality of Tangwei capsule to provide laboratory support for its quality control and overall evaluation.

Factores diferenciales entre desistimiento individual y colectivo de mujeres de las FARC-EP en prisión / Differential factors between individual and collective desistance of FARC-EP women in prison / Fatores diferenciais entre a desistência individual e coletiva das mulheres das FARC-EP na prisão

Para el año 2017 se encontraban vigentes en Colombia dos marcos jurídicos para promover el desistimiento y desarticulación de las FARC-EP. Los dos, aunque desde contextos diferentes, han promovido, por un lado, el desistimiento individual y por otro, el desistimiento colectivo de sus miembros. Las mujeres han sido partícipes de ambos procesos, desde la libertad o la prisión de manera minoritaria y asimétrica en comparación con los hombres. Con el interés de analizar este fenómeno, el presente estudio buscó identificar los factores que llevaron a las mujeres a desistir según una u otra modalidad y de-terminar diferencias y similitudes. Para este propósito se diseñó un modelo probabilístico que captara las relaciones de causalidad entre desistimiento y factores predichos desde las teorías del aprendizaje social, de la elección racional y del control social informal, en una muestra de mujeres farianas en prisión que desistieron de forma individual y colectiva. Se encontró que factores como pertenecer a un rango de edad entre 20 y 31 años, tener pareja y haber participado en delitos graves, asociados al terrorismo, influyeron en la selección de la modalidad individual, mientras que tener más de 31 años, participar en delitos comunes junto a los asociados con el terrorismo, incluyendo el narcotráfico, y proceder de regiones con historia de conflicto arraigada predijeron el desistimiento colectivo.

By 2017, there were two legal frameworks in force in Colombia to promote the disbanding and dismantling of the FARC-EP. Both, although from different contexts, have promoted, on the one hand, the individual disbandment and, on the other, the collective disbandment of its members. Women have participated in both processes, from freedom or prison, in a minority and asymmetrical manner compared to men. In order to analyse this phenomenon, this study sought to identify the factors that led women to desist in one or the other modality and to determine differences and similarities. For this purpose, a probabilistic model was designed to capture the causal relationships between desistance and factors predicted from the theories of social learning, rational choice and informal social control, in a sample of women in prison who desisted individually and collectively. It was found that factors such as belonging to an age range between 20 and 31 years, having a partner and having participated in serious crimes associated with terrorism, influenced the selection of the individual modality, while being over 31 years old, participating in common crimes along with those associated with terrorism, including drug trafficking, and coming from regions with a history of deep-rooted conflict predicted collective desistance.

Até 2017, havia duas estruturas legais em vigor na Colômbia para promover a dissolução e o desmantelamento das FARC-EP. Ambos, embora de contextos diferentes, têm promovido, por um lado, a dissolução individual e, por outro, a dissolução coletiva de seus membros. As mulheres participaram de ambos os processos, da liberdade ou da prisão, de forma minoritária e assimétrica em relação aos homens. A fim de analisar este fenômeno, este estudo procurou identificar os fatores que levaram as mulheres a desistir em uma ou outra modalidade e determinar diferenças e semelhanças. Para este fim, um modelo probabilístico foi projetado para capturar as relações causais entre a desistência e os fatores previstos a partir das teorias de aprendizagem social, escolha racional e controle social informal, em uma amostra de mulheres na prisão que desistiram individual e coletivamente. Constatou-se que fatores como pertencer a uma faixa etária entre 20 e 31 anos, ter um parceiro e ter participado de crimes graves associados ao terrorismo, influenciaram a seleção da modalidade individual, embora tendo mais de 31 anos de idade, participar de crimes comuns juntamente com aqueles associados ao terrorismo, incluindo o tráfico de drogas, e vindo de regiões com um histórico de conflitos profundamente enraizados preveram a desistência coletiva.

Superexploração da força de trabalho: uma proposta metodológica de análise / Superexploitation of the labor force: a methodological proposal for analysis

Resumo: O presente ensaio propõe uma análise quantitativa da superexploração da força de trabalho, especialmente por meio de mecanismos que vinculem a intensificação da exploração da força de trabalho às transferências estruturais de valor da periferia ao centro. Nosso propósito é esboçar breves notas metodológicas que contribuam com os esforços incipientes de análise quantitativa da superexploração, avançando em relação a eles, sobretudo mediante o reconhecimento dos limites desses esforços.

Abstract: This essay proposes a quantitative analysis of the superexploitation of the labor force, especially through mechanisms that link the intensification of the exploitation of the labor force to structural transfers of value from the periphery to the center. Our purpose is to outline brief methodological notes that contribute to the incipient efforts of quantitative analysis of superexploitation, moving forward in relation to them, especially based on a recognition of the limits of these efforts.

Simultaneous determination of five components in Forsythia suspensa flower with UPLC-QAMS / 中国药房

OBJECTIVE To establish the methods for simultaneous determination of rutin， forsythiaside A， （+）-pinoresinol-4- O-β-D-glucopyranoside， forsythin and forsythigenin in Forsythia suspensa flower. METHODS UPLC method was adopted. The determination was performed on ACQUITY UPLC HSS T3 C18 column with mobile phase consisted of acetonitrile-0.1% phosphoric acid solution （gradient elution） at the flow rate of 0.3 mL/min. The detection wavelengths were set at 275 nm （0-8 min），330 nm （8-10.5 min），275 nm （10.5-32 min）， respectively. The column temperature was 25 ℃， and sample size was 1 μL. Taking rutin as reference， the content of each component was determined by quantitative analysis of multi-components by single-marker （QAMS） method， and then compared with external standard method. RESULTS The contents of forsythiaside A， （+）-pinoresinol-4-O-β-D- glucopyranoside， forsythin and forsythigenin by QAMS were 7.472-7.671， 2.919-2.986， 1.439-1.486， 1.523-1.566 mg/g； the results obtained by the external standard method were 7.454-7.664， 2.913-2.996， 1.444-1.484， 1.519-1.562 mg/g， respectively. There was no significant difference in the measurement results between the two methods， with a relative deviation less than 1.0%. CONCLUSIONS This study successfully establishes the UPLC-QAMS method for simultaneous determination of five components in F. suspensa flower， and the results obtained by this method are not significantly different from those obtained by the external standard method. It can be used for quality control of F. suspensa flower.

Establishment of quantitative analysis of multi-components by single marker for content determination of 10 ganoderic acids in Ganoderma lucidum / 中国药房

OBJECTIVE To establish a quantitative analysis of multi-components by single marker （QAMS） method for simultaneous determination of 10 ganoderic acids in Ganoderma lucidum. METHODS Using ganoderic acid A as internal reference， high-performance liquid chromatography （HPLC） method was adopted to calculate relative correction factors of the other 9 components， such as ganoderic acid B， ganoderic acid C2， ganoderic acid D， ganoderic acid F， ganoderic acid H， ganoderenic acid A， ganoderenic acid B， ganoderenic acid C， ganoderenic acid D； the contents of above ganoderic acids were calculated with relative correction factors， and compared with the results of external standard method. RESULTS The linear relationship of ganoderic acid A， ganoderic acid B， ganoderic acid C2， ganoderic acid D， ganoderic acid F， ganoderic acid H， ganoderenic acid A， ganoderenic acid B， ganoderenic acid C and ganoderenic acid D were 0.032-3.996， 0.040-4.971， 0.037-4.568， 0.028-3.558， 0.033-4.177， 0.044-5.440， 0.032-3.944， 0.040-4.994， 0.045-5.593 and 0.035-4.342 mg/mL （all R 2≥0.999 2）， respectively. RSDs of precision， stability （24 h） and reproducibility tests were all lower than 2%. Their average recovery rates were 99.43%， 100.25%， 98.50%， 99.88%， 100.59%， 99.64%， 98.50%， 99.40%， 99.64% and 99.76%， respectively （RSD＜2%， n＝6）. Relative correction factors of ganoderic acid B， ganoderic acid C2， ganoderic acid D， ganoderic acid F， ganoderic acid H， ganoderenic acid A， ganoderenic acid B， ganoderenic acid C and ganoderenic acid D were 1.788 5， 1.288 2， 1.126 4， 1.698 5， 0.885 4， 5.468 1， 4.210 9， 5.780 8， 4.290 3， respectively. Relative errors between the content obtained by QAMS method and external standard method for G. lucidum from different origins were within ±12%. CONCLUSIONS It is feasible that the contents of 10 ganoderic acids are determined simultaneously by QAMS method， using ganoderic acid A as internal reference. This method shows good precision and reproducibility and can be used for the quality control of G. lucidum.

Infrared spectral band screening based on partial least squares is used for the quantitative analysis of mannitol-calcium chloride cocrystal / 药学学报

Mannitol-calcium chloride metal organic framework (MOF) cocrystal significantly improved the tabletability of β-mannitol and could be developed as a new tablet filler. However, mannitol monomer was found in the product during the scale-up production of the excipient, which significantly affected the functional properties of the excipient. In this study, we intend to quantify the multi-component eutectic system of mannitol-calcium chloride. In this experiment, the MOF cocrystal excipient mannitol-calcium chloride cocrystal was used as the model compound, and infrared spectrum was collected. Based on partial least squares regression (PLSR) method, the abnormal bands were removed and the spectrum was preprocessed by normalization. The quantitative correction model of mannitol-calcium chloride MOF cocrystal content in cocrystal excipients was established and compared by two different variable screening methods, genetic algorithm (GA) and competitive adaptive reweighting algorithm (CARS). Two different variable screening methods, GA method and CARS method, were used to screen out 160 and 14 variables, respectively. The mannitol-calcium chloride cocrystal model established by CARS-PLSR method had the best performance, and the average relative error (MRE) and corrected root mean square error (RMSEC) of the model were 0.008 8 and 0.892 5, respectively, the determination coefficient (R2) of the model was increased from 0.978 3 to 0.994 4. The quantitative method of eutectic system established in this study has high prediction accuracy, fast detection speed and good stability, which is of great significance for optimizing the preparation process conditions and quality control methods of such eutectic excipients.

The PK bioanalysis method study of c-Met antibody-drug conjugate (RC108) in cynomolgus monkey / 药学学报

Antibody-drug conjugate (ADC) has the characteristics of low toxicity and high efficiency, and plays an important role in cancer treatment. However, due to the complexity of its structure, it brings difficulties in pharmacokinetic (PK) bioanalysis. This study established an analytical method for the detection of ADC (RC108) in cynomolgus monkey plasma by ligand-binding assay (LBA) and liquid chromatography tandem mass spectrometry (LC-MS/MS), which was used to analyze and quantify the total antibody, bound antibody and free drug in cynomolgus monkey plasma. Based on the LBA method, rabbit anti-RC108 Fab and mouse anti-MMAE (monomethyl auristatin E) mAb were pre-coated in 96-well plates as the total antibody and antibody binding reagents, respectively. The samples to be tested were added, and then the detection reagents were added in turn. Goat anti-human IgG (H+L)-HRP, chromogenic solution tetramethylbenzidine (TMB), H2SO4 terminate the reaction, read data at 450 nm/630 nm wavelength of microplate reader; LC-MS/MS analysis method quantifies MMAE concentration, and refer to relevant regulations for methodological validation. The analytical method for quantifying total antibody, bound antibody and free drug of RC108 drug obtained good accuracy and precision, and the selectivity, dilution linearity, hook effect, parallelism and stability were verified. Meet the requirements of biological analysis. Finally, a bioanalytical method for the determination of the concentration of the test substance RC108 (total antibody, conjugated antibody, free MMAE) in cynomolgus monkey plasma with high sensitivity and high throughput was established by LBA and LC-MS/MS method. Subsequent non-clinical research on PK research in cynomolgus monkeys will provide technical support.

Analysis on Quality Standard of Fraxini Cortex（Fraxinus chinensis） Dispensing Granules Based on Standard Decoction / 中国实验方剂学杂志

ObjectiveTo establish the quality standard for Fraxini Cortex（Fraxinus chinensis） dispensing granules based on standard decoction， and to provide a basis for the quality control of this dispensing granules. MethodHigh performance liquid chromatography（HPLC） specific chromatograms of 15 batches of Fraxini Cortex（F. chinensis） standard decoctions and 3 batches of Fraxini Cortex（F. chinensis） dispensing granules were established with the mobile phase of 0.1% phosphoric acid aqueous solution（A）-acetonitrile（B） for gradient elution（0-10 min， 12%-15%B； 10-30 min， 15%-32%B） and the detection wavelength of 220 nm. And similarity evaluation， cluster analysis and principal component analysis（PCA） were also carried out. HPLC quantitative analysis of multi-components by single marker（QAMS） was established to determine the contents of the main components in the standard decoctions and dispensing granules. The contents of the corresponding components in Fraxini Cortex（F. chinensis） decoction pieces were also detected， and the transfer rates from decoction pieces to standard decoctions and dispensing granules were calculated. ResultThe similarities between specific chromatograms of 15 batches of Fraxini Cortex（F. chinensis） standard decoctions and 3 batches of Fraxini Cortex（F. chinensis） dispensing granules were all>0.9， and 7 common peaks were identified. The results of cluster analysis and PCA showed that there was some differences in the composition of different batches of standard decoctions， but did not show aggregation of origin. As the standard decoctions， the extract rate was 6.18%-11.62%， the contents of esculin， syringin， fraxin， esculetin， fraxetin， calceolarioside B were 44.92-103.51， 1.36-11.87， 33.26-90.73， 4.63-29.75， 2.40-16.86， 2.49-17.35 mg·g-1， and the transfer rates from decoction pieces to standard decoction were 25.21%-42.54%， 52.57%-88.84%， 43.43%-79.45%， 49.15%-88.27%， 49.22%-72.69%， 27.66%-47.67%， respectively. The extract rates of Fraxini Cortex（F. chinensis） dispensing granules were 10.4%-10.7%， the transfer rates of the above six components from decoction pieces to dispensing granules were 42.76%-43.17%， 80.01%-80.90%， 59.59%-59.88%， 51.35%-52.67%， 60.50%-60.93%， 37.98%-38.37%， respectively， which were generally consistent with the transfer rates from decoction pieces to standard decoctions. ConclusionThe established quality control standard of Fraxini Cortex（F. chinensis） dispensing granules based on standard decoctions is reasonable and reliable， which can provide reference for the quality control and process research of this dispensing granules.

Study on quality control method of Qiguiling mixture / 中国药房

OBJECTIVE To establish the fingerprint of Qiguiling mixture and the method for the content determination of 4 kinds of active components such as calycosin-7-glucoside， so as to control the quality of Qiguiling mixture. METHODS The fingerprints of 12 batches of Qiguiling mixture were established by HPLC. SPSS 25.0 software was used for cluster analysis and principal component analysis， and SIMCA 14.1 software was used for orthogonal partial least squares-discriminant analysis. The variable importance in projection （VIP） value greater than 1.0 was used as the index to screen the differential components. The contents of calycosin-7-glucoside， glycyrrhizin and glycyrrhizic acid were calculated by the quantitative analysis of multi- components by single marker （QAMS） with hesperidin as the internal reference， and the results were compared with external standard method. RESULTS In the fingerprints of 12 batches of samples， 17 common peaks were identified， and the similarities were more than 0.940. A total of 4 common peaks were identified， which were calycosin-7-glucoside （peak 6）， glycyrrhizin （peak 8）， hesperidin （peak 12）， and glycyrrhizic acid （peak 17）. The 12 batches of samples could be clustered into two categories， S4， S7-S9 and S11-S12 were clustered into one category， and the other batches of samples were clustered into one category. The cumulative variance contribution rate of the six principal components was 85.840%， and VIP values of peaks 15， 14， 4， 8 （glycyrrhizin） and 9 were all greater than 1.0. The relative error between the results of QAMS and external standard method was less than 5% （n＝3） for the contents of calycosin-7-glucoside， glycyrrhizin and glycyrrhizic acid. CONCLUSIONS Established HPLC fingerprint and content determination method in this study can be used for quality control of Qigiling mixture. Five components such as glycyrrhizin are the differential components.

Quality control of Portulaca oleracea by HPLC fingerprint combined with quantitative analysis of multi-components by single-marker / 中国药房

OBJECTIVE To establish HPLC fingerprint of Portulaca oleracea， establish quantitative analysis of multi- components by single-marker （QAMS） method for the content determination of caffeic acid， ferulic acid， genistin and quercetin， and provide reference for quality control of the medicine. METHODS The determination was performed on Eclipse XDB-C18 column with mobile phase consisted of methanol-0.2% phosphoric acid solution （gradient elution） at the flow rate of 1.0 mL/min. The column temperature was 25 °C， and detection wavelength was set at 360 nm. The sample size was 10 μL. HPLC fingerprint of P. oleracea was established according to the above chromatographic conditions. Cluster analysis （CA） and principal component analysis （PCA） were performed for 15 batches of specimens. Using caffeic acid as internal standard， relative correction factors of other three components were calculated by QAMS， and then the component content was calculated on the basis of relative correction factors， which was compared with the external standard method. RESULTS HPLC fingerprints of 15 batches of P. oleracea were calibrated with a total of 17 common peaks， and 4 components （caffeic acid， ferulic acid， genistin， quercetin） were identified； the similarities of 15 batches of samples were greater than 0.890. The results of CA showed that S1-S10 were clustered into one category， and S11-S15 were clustered into one category. The results of PCA revealed that the accumulative contribution rate of the two main components was 92.502%， and the classification results were basically consistent with CA. The linear range of caffeic acid， ferulic acid， genistin and quercetin were 0.003 1-0.157 1， 0.003 6-0.181 7， 0.008 5-0.425 6，0.000 4-0.021 8 mg/mL （R2≥0.999 7）； the results of precision， repeatability， stability （24 h） and recovery tests all complied with the requirements of Chinese Pharmacopoeia. The relative correction factors of ferulic acid， genistin and quercetin calculated by QAMS were 1.534， 5.302 and 0.174； there was no significant difference in the contents of components measured between this method and the external standard method. CONCLUSIONS The established HPLC fingerprint combined with QAMS can be used for the quality control of multiple index components in P. oleracea. The origin has a certain influence on the quality of P. oleracea， and the quality of P. oleracea produced in Sichuan is better than that produced in Anhui and Hebei.

An emerging analytical tool for highly sensitive quantitative analysis based on liquid chromatography-multiple-reaction monitoring cubed (MRM3) / 中国药科大学学报

@#Liquid chromatography-multiple-reaction monitoring (LC-MRM) has been widely recognized as the golden standard for multiple components-targeted quantitative analysis of complicated matrices,with extensive applications for analysis in such fields as chemical drugs, traditional Chinese medicines and foods.Unfortunately, when facing the task of quantitatively analyzing trace chemical components in complex matrices, MRM suffers dramatically from the background noise or matrix interference, leading to undesirable sensitivity and selectivity in terms of the lower limits of quantification (LOQ) and detection (LOD).In recent years, MRM cubed (MRM3), also known as MS3 scan, has received much attention because of its unique ability to significantly improve detection selectivity and sensitivity attributing to the successive ion filtering function, enabling LC-MRM3 as an emerging analytical tool.In this review,our attention is devoted to: 1) the illustration of the principle for MRM3; 2) parameter settings; and 3) the application progress of LC-MRM3 in such fields as the pursuit of biomarkers, pharmaceutical analysis, forensic analysis, toxicological analysis, food chemistry, and environmental analysis, aiming to provide a promising analytical tool of LC-MRM3 advantageous in the quantification analysis of trace chemical components in complex matrices.

Simultaneous determination of fifteen components in Niuhuang Jiangya Pills by UPLC-Q Exactive-Orbitrap MS / 药学学报

An ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry (UPLC-Q Exactive-Orbitrap MS) method for the simultaneous determination of 15 compounds (taurocholic acid, 7-keto-3α,12-α-dihydroxycholanic acid, glycocholic acid, 3-oxo-7α,12α-hydroxy-5β-cholanoic acid, taurochenodeoxycholic acid, 3α-hydroxy-7-oxo-5β-cholanic acid, hyocholic acid, sodium taurodeoxycholate, hyodeoxycholic acid, cholic acid, glycochenodeoxycholic acid, glycodeoxycholic acid, taurolithocholic acid sodium salt, chenodeoxycholic acid, deoxycholic acid) in Niuhuang Jiangya Pills was established. The separation was performed on a Thermo Fisher Scientfic Bremen HYPERSIL GOLD C18 column (100 mm × 2.1 mm, 1.9 μm). Methanol and water (containing 0.1% formic acid)were adopted as the mobile phase by gradient elution．MS detection was performed with multiple reaction monitoring mode．The results showed that fifteen compounds had a good linearity within their respective concentration ranges (r > 0.999 0). The average recovery rates were 93.7%- 105.2% (n = 9). The established method was used to determine the content of 15 batches of samples, and the results showed that the content of cholic acid was quite different. The present study provides an important reference for the overall quality control of Niuhuang Jiangya Pills.

Simultaneous determination of seven different components in Cynomorium songaricum Rupr. by QAMS / 药学学报

A quantitative analysis of multi-components by single marker method (QAMS) was established for simultaneous determination of gallic acid, protocatechuic acid, catechin, epicatechin, p-coumaric acid, ferulic acid and phloridzin in Cynomorium songaricum Rupr. The analysis was performed on a ChromCore Polae C18 column (250 mm×4.6 mm, 5 μm) , with a mobile phase consisting of acetonitrile-0.3% phosphoric acid aqueous solution for gradient elution. The volume flow rate, column temperature and sample injection volume were set at 1.0 mL·min-1, 25 ℃, and 40 µL, respectively. The relative correction factors of gallic acid and protocatechuic acid, catechin, epicatechin, p-coumaric acid, ferulic acid and phloridzin were calculated and the durability was also investigated. The contents of these seven compounds in fourteen batches of Cynomorium songaricum Rupr. from different producing areas or batches were determined by external standard method (ESM) and quantitative analysis of multi-components with a single-marker method (QAMS), respectively. SPSS and Origin Pro software were employed for principal components assay, similarity evaluation and cluster analysis. The specificity, precision, repeatability, stability and linear range (R2 > 0.999 0) of the seven components were all good. The average recovery was 96.89%-103.16% and RSD was 0.55%-2.76%. Then gallic acid was chosen as internal reference for calculation the correction factors for the other six components, the average relative correction factors of protocatechuic acid, catechin, epicatechin, p-coumaric acid, ferulic acid and phloridzin were 1.141 5, 0.200 5, 0.208 0, 2.361 9, 1.867 7, 0.204 6, respectively. Student's test results showed that there was no significant difference between the data analyzed by ESM and the data obtained from QAMS method. Through data visualization analysis, the contents of gallic acid, protocatechuic acid, catechin and epicatechin in different samples were significantly different, indicating that these four components might be the main quality markers of Cynomorium songaricum Rupr. for gaving more contributes to the principal components. The cluster analysis showed that samples from Xinjiang and samples from Inner Mongolia were clustered in significantly different categories, meaning that the quality of Cynomorium songaricum Rupr. had great relation with producing areas. The method of QAMS established in this study is a simple, economical and practical method with scientific and applicable charactistics for evaluating the quality of Cynomorium songaricum Rupr. efficiently and scientifically.