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[Display omitted] • Carrier-free delivery systems of pyrimethanil (PYR) were constructed through supramolecular self-assembly. • PYR nano cocrystal suspensions (NCSs) exhibited excellent photostability, thermal stability, and volatile stability. • PYR NCS demonstrated sustained-release properties and exhibited excellent long-term antifungal activity against Botrytis cinerea. The adverse effects resulting from off-target pesticide application pose significant risks to both ecosystems and public health. Therefore, developing a pesticide delivery system that is straightforward, effective, and devoid of secondary pollution is crucial for environmental safety. Herein, self-assembled crystalline materials involved pyrimethanil (PYR) and organic acids were constructed by crystal engineering. These materials allowed for direct manipulation of the physicochemical properties and environmental fate of PYR by the building modules. The melting point of PYR was increased from 96.19 °C to 206.69 °C. The photostability and volatile stability were improved by 3.85-fold and 297-fold, respectively. Afterwards, these crystalline materials were prepared as nano cocrystal suspensions (NCSs) in water by the one-pot method. The PYR NCSs exhibited potent bioactivity against Botrytis cinerea and demonstrated slow-release behavior. Upon foliar spraying, the PYR NCSs exhibited desirable foliar wettability with a contact angle lower than 36°. By limiting leaching into the soil and reducing environmental pesticide exposure, PYR NCS ensured the safety of both earthworms and plants. The structure–property relationships of PYR NCSs were elucidated through intermolecular interaction analysis and theoretical calculations. Overall, the NCSs constructed by the supramolecular chemistry strategy are characterized by the simple preparation, high bioactivity, stability, no carrier, slow-release, and minimal environmental risk, which offers insight for improving the utilization and sustainable management of pesticides. [ABSTRACT FROM AUTHOR]

Chemical imaging (CI) possesses a strong ability of pharmaceutical analysis. Its great strength relies on the integration of traditional spectroscopy (one dimension) and imaging technique (two dimensions) to generate three-dimensional data hypercubes. Data pre-processing or processing methods are proposed to analyze vast data matrixes and thereby realizing different research objectives. In this review paper, various pharmaceutical applications of quality control over the past few years are summed up in two groups of final product test and industrial utilization. The scope of "quality control" here includes traditional analytical use, process understanding and manufactural control. Finally, two major challenges about undesirable sample geometry and lengthy acquisition time are discussed for prospective commercial or industrial application. [ABSTRACT FROM AUTHOR]

[Display omitted] • Smart pesticide delivery system was constructed based on cocrystal engineering. • PYR-TM@TA-Cu exhibited pH-responsive properties and photostability. • Metal phenolic network provided nanocapsules better adhesion and wettability. • PYR-TM@TA-Cu showed better biosafety and bioactivity. Pesticides have always been restricted by environmental factors and utilization rate. Smart delivery systems are important to modify pesticides and improve utilization rate, but the economic and environmental risks of the carriers limit their practical applications. Here, responsive release nanocapsules were constructed with metal-phenolic networks and pyraclostrobin - thiophanate-methyl (PYR-TM) cocrystal core to modify the poor physicochemical properties and safety of pesticides. PYR-TM was prepared by sustainable mechanochemical method and deposited by metal-phenolic networks in water, producing the PYR-TM@TA-Cu nanocapsules. The crystal structure and DFT calculations proved that TM improved the photostability of PYR by 75.7-fold through competitive energy absorption of photon and molecular conformation modulation. With a loading capacity up to 91.2%, PYR-TM@TA-Cu exhibited pH-responsive release behavior triggered by acidic conditions, which showed that 43.6%, 51.4%, 62.4% and 81.6% of encapsulated PYR were released at pH 7.9, 6.2, 5.3, and 4.0, respectively. Additionally, PYR-TM@TA-Cu exhibited favorable fungicidal activity (EC 50 = 0.123 mg/L) in controlling Botrytis cinerea. The greenhouse control efficiency of fungal infection was enhanced from12.0% to 70.7% by PYR-TM@TA-Cu after 7 days spraying. The coating of metal-phenolic network improved the washing persistence of the pesticides from 51.26% to 79.88%, the security for zebrafish by 42-fold, and decreased the leaching potential of the pesticides. Meanwhile, PYR-TM@TA-Cu showed no phytotoxicity on the growth of corn and cucumber plants. Overall, this study provides insight into efficient and sustainable agricultural production with the construction of an eco-friendly nanocapsules platform by cocrystal engineering strategy. [ABSTRACT FROM AUTHOR]

Seed vigor is influenced by seed position in plant. However, current understanding of its underlying mechanism is limited. In this study, we used isobaric tags for relative and absolute quantitation technique to study the comparative proteomes between middle seeds (with higher vigor) and top seeds of maize (Zea mays L.) ears at 0 h, 24 h, and 48 h of imbibition. A total of 159 differentially accumulated proteins were identified. Among these, the largest number of proteins was from the functional categories of Disease/Defense and Metabolism. Compared with top seeds, most of the differentially accumulated proteins of Protein Synthesis and Energy showed higher accumulation in middle seeds at 0 h and 24 h of imbibition, but lower accumulation at 48 h of imbibition. Seed water absorption activates metabolic processes. The water content of middle seeds was significantly lower than that of top seeds at between 12 h and 30 h of imbibition, but energy production would be higher in the middle seeds at 24 h of imbibition. Meanwhile, tonoplast intrinsic proteins 3.1 and 3.2, which mediate water inflow into protein storage vacuoles, then activating enzymes involved in reserve mobilization, showed higher accumulation in middle seeds at 24 h of imbibition. In addition, our data also showed middle seeds may suffer less fungal damages. Our results contribute to understanding the mechanisms underlying the effects of growth position on seed vigor. [ABSTRACT FROM AUTHOR]

As unsafe components in herbal medicine (HM), saccharides can affect not only the drug appearance and stabilization, but also the drug efficacy and safety. The present study focuses on the in-line monitoring of batch alcohol precipitation processes for saccharide removal using near-infrared (NIR) spectroscopy. NIR spectra in the 4000–10,000-cm − 1 wavelength range are acquired in situ using a transflectance probe. These directly acquired spectra allow characterization of the dynamic variation tendency of saccharides during alcohol precipitation. Calibration models based on partial least squares (PLS) regression have been developed for the three saccharide impurities, namely glucose, fructose, and sucrose. Model errors are estimated as the root-mean-square errors of cross-validation (RMSECVs) of internal validation and root-mean-square errors of prediction (RMSEPs) of external validation. The RMSECV values of glucose, fructose, and sucrose were 1.150, 1.535, and 3.067 mg ⋅ mL − 1 , and the RMSEP values were 0.711, 1.547, and 3.740 mg ⋅ mL − 1 , respectively. The correlation coefficients (r) between the NIR predictive and the reference measurement values were all above 0.94. Furthermore, NIR predictions based on the constructed models improved our understanding of sugar removal and helped develop a control strategy for alcohol precipitation. The results demonstrate that, as an alternative process analytical technology (PAT) tool for monitoring batch alcohol precipitation processes, NIR spectroscopy is advantageous for both efficient determination of quality characteristics (fast, in situ, and requiring no toxic reagents) and process stability, and evaluating the repeatability. [ABSTRACT FROM AUTHOR]

Charged aerosol detection, increasingly recognized for quantifying pharmaceutical compounds with weak ultraviolet absorption, is a universal detection technique for high‐performance liquid chromatography (HPLC). Charged aerosol detection shows a non‐linear response with increasing analyte concentration over a wide range, limiting its versatility in various analytical applications. In this work, a co‐optimization strategy for power function value (PFV) and power laws was proposed and applied to broaden the linear range of the standard curve of saccharides in Qishen Yiqi dripping pills using the HPLC‐charged aerosol detection (HPLC‐CAD) method. Power function values for all analytes were optimized based on empirical models. Subsequently, the optimum power laws were investigated based on a preferred PFV. Additionally, various regression equations were evaluated to ensure the accuracy and precision of the results. With the optimized PFV and power law, the ordinary least squares model demonstrated a satisfactory fit. The optimal PFVs and power laws expanded the standard curve's linear range by 2.7 times compared to default settings, reducing model uncertainty. This paper presents a vital method for developing a multi‐component quantitative HPLC‐CAD approach without external data transformation outside the provided software, especially suitable for analytical applications of traditional Chinese medicine with significant quality differences. [ABSTRACT FROM AUTHOR]

[Display omitted] • Mechanochemical synthesis of multi-component crystals of the natural antibiotic magnolol. • Enhanced dissolution properties lead to increased antibacterial activity. • Construct of structure–activity relationship and managing of multi-component crystal on physicochemical properties. • Design of isostructural cocrystal and evaluation of pharmaceutical properties. Antibiotic is one of the most important discoveries in human and animal medicine. However, the inefficient use of antibiotics has caused widespread and persistent contamination of ecosystems, setting off microbial resistance storms. Magnolol is a botanical antibiotic, but poor physicochemical properties result in low bioavailability. Increasing solubility of magnolol can help to reduce the doses of medications to patients, minimize bothersome side effects. In this work, three novel multicomponent crystalline solids were synthesized from magnolol and isomeric coformers by mechanochemistry. It was found that the multicomponent crystalline solids achieved the customizable release profile of magnolol by manipulating the substituent positions of the isomers and complexation. Antibacterial activity test showed that bioactivity on two bacteria was considerably improved by designed MGN multicomponent crystals. In addition, the coformers controlled the dissolution behavior and further stabilized the improvement according to the variable statistical analysis. In conclusion, the properties of antibiotic multicomponent solids can be manipulated through the coformers. This provides an effective strategy for managing the release of drugs to meet individual biological differences and diverse therapeutic needs. [ABSTRACT FROM AUTHOR]

A method combining solid phase extraction, high performance liquid chromatography, and ultraviolet/evaporative light scattering detection (SPE-HPLC-UV/ELSD) was developed according to Quality by Design (QbD) principles and used to assay nine bioactive compounds within a botanical drug, Shenqi Fuzheng Injection. Risk assessment and a Plackett-Burman design were utilized to evaluate the impact of 11 factors on the resolutions and signal-to-noise of chromatographic peaks. Multiple regression and Pareto ranking analysis indicated that the sorbent mass, sample volume, flow rate, column temperature, evaporator temperature, and gas flow rate were statistically significant ( p < 0.05) in this procedure. Furthermore, a Box-Behnken design combined with response surface analysis was employed to study the relationships between the quality of SPE-HPLC-UV/ELSD analysis and four significant factors, i.e., flow rate, column temperature, evaporator temperature, and gas flow rate. An analytical design space of SPE-HPLC-UV/ELSD was then constructed by calculated Monte Carlo probability. In the presented approach, the operating parameters of sample preparation, chromatographic separation, and compound detection were investigated simultaneously. Eight terms of method validation, i.e., system-suitability tests, method robustness/ruggedness, sensitivity, precision, repeatability, linearity, accuracy, and stability, were accomplished at a selected working point. These results revealed that the QbD principles were suitable in the development of analytical procedures for samples in complex matrices. Meanwhile, the analytical quality and method robustness were validated by the analytical design space. The presented strategy provides a tutorial on the development of a robust QbD-compliant quantitative method for samples in complex matrices. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Near infrared spectroscopy combined with chemometrics was investigated for the fast determination of total organic carbon (TOC) and soluble solids contents (SSC) of Tanreqing injection intermediates. The NIR spectra were collected in transflective mode, and the TOC and SSC reference values were determined with Multi N/C UV HS analyzer and loss on drying method. The samples were divided into calibration sets and validation sets using the Kennard–Stone (KS) algorithm. The Dixon test, leverage and studentized residual test were studied for the sample outlier analysis. The selection of wavebands, spectra pretreated method and the number of latent variables were optimized to obtain better results. The quantitative calibration models were established with 3 different PLS regression algorithms, named linear PLS, non-linear PLS and concentration weighted PLS, and the net result was defined as the average of the predicted values of the different calibration models. The overall results indicated that the presented method is more powerful than single multivariable regression method, characterized by higher mean recovery rate (MRR) of the validation set, and can be used for the rapid determination of TOC and SSC values of Tanreqing injection intermediates, which are two important quality indicators for the process monitoring. [ABSTRACT FROM AUTHOR]

Percolation is a common extraction method of food processing industry. In this work, taking the percolation extraction of salvianolic acid B from Salvia miltiorrhiza (Salviae Miltiorrhizae Radix et Rhizoma) as an example, the percolation mechanism model was derived. The volume partition coefficient was calculated according to the impregnation. experiment. The bed layer voidage was measured by single-factor percolation experiment and the internal mass transfer coefficient was calculated by the parameters obtained by fitting the impregnation kinetic model. After screening, the Wilson and Geankoplis, and Koch and Brady formulas were used to calculate the external mass transfer coefficient and the axial diffusion coefficient, respectively. After substituting each parameter into the model, the process of percolation of Salvia miltiorrhiza was predicted, and the coefficient of determination R2 was all greater than 0.94. Sensitivity analysis was used to show that all the parameters studied had a significant impact on the prediction effect. Based on the model, the design space including the range of raw material properties and process parameters was established and successfully verified. At the same time, the model was applied to the quantitative extraction and endpoint prediction of the percolation process. [ABSTRACT FROM AUTHOR]

The step of enriching and purifying saponins by macroporous resin column chromatography is closely related to the safety and efficacy of Panax notoginseng products during their manufacturing processes. Adsorption process is one of the most critical unit operations within each chromatographic cycle. In order to understand the adsorption process directly, it is necessary to develop a rapid and precise method to monitor the adsorption process in real time. In this study, comparative evaluation of using near-infrared (NIR) spectra, ultraviolet (UV) spectra and fused spectra to monitor the adsorption process of P. notoginseng was conducted. The uninformative variable elimination by partial least squares (UVE-PLS) regression models were established for quantification of notoginsenoside R 1 , ginsenoside Rg 1 , ginsenoside Re, ginsenoside Rb 1 and ginsenoside Rd in effluents based on different spectra. There was a significant improvement provided by the models based on fused spectra. The results in this work were conducive to solving the problems about real-time quantitative analysis of saponins during P. notoginseng adsorption. The fusion method of NIR and UV spectra combined with UVE-PLS regression could be a promising strategy to real-time analyze the components, which are difficult to be quantified by individual spectroscopic technique. [ABSTRACT FROM AUTHOR]

Homogeneity of powder blend is essential to obtain uniform contents for the tablets and capsules. Near-infrared (NIR) spectroscopy with fiber-optic probe was used as an on-line technique for monitoring the homogeneity of pharmaceutical blend during the blending process instead of the traditional techniques, such as high performance liquid chromatograph (HPLC) method. In this paper NIRS with a SabIR diffuse reflectance fiber-optic probe was used to monitor the blending process of coptis powder and lactose (excipient) with different contents, and further qualitative methods, like similarity, moving block of standard deviation and mean square were used for calculation purposes with the collected spectra after the pretreatment of multiplicative signal correction (MSC) and second derivative. Correlation spectrum was used for the wavelength selection. Four different coptis were blended with lactose separately to validate the proposed method, and the blending process of "liu wei di huang" pill was also simulated in bottles to verify this method on multiple herbal blends. The overall results suggest that NIRS is a simple, effective and noninvasive technique can be successfully applied to the determination of homogeneity in the herbal blend. [ABSTRACT FROM AUTHOR]

A discriminant analysis technique using wavelet transformation (WT) and influence matrix analysis (CAIMAN) method is proposed for the near infrared (NIR) spectroscopy classification. In the proposed methodology, NIR spectra are decomposed by WT for data compression and a forward feature selection is further employed to extract the relevant information from the wavelet coefficients, reducing both classification errors and model complexity. A discriminant-CAIMAN (D-CAIMAN) method is utilized to build the classification model in wavelet domain on the basis of reduced wavelet coefficients of spectral variables. NIR spectra data set of 265 salviae miltiorrhizae radix samples from 9 different geographical origins is used as an example to test the classification performance of the algorithm. For a comparison, k-nearest neighbor (KNN), linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA) methods are also employed. D-CAIMAN with wavelet-based feature selection (WD-CAIMAN) method shows the best performance, achieving the total classification rate of 100% in both cross-validation set and prediction set. It is worth noting that the WD-CAIMAN classifier also shows improved sensitivity, selectivity and model interpretability in the classifications. [ABSTRACT FROM AUTHOR]

Abstract: Fluid bed is an important unit operation in pharmaceutical industry for granulation and drying. To improve our understanding of fluid bed granulation, in-line near infrared spectroscopy (NIRS) and novel environmental temperature and RH data logger called a PyroButton® were used in conjunction with partial least square (PLS) and principal component analysis (PCA) to develop multivariate statistical process control charts (MSPC). These control charts were constructed using real-time moisture, temperature and humidity data obtained from batch experiments. To demonstrate their application, statistical control charts such as Scores, Distance to model (DModX), and Hotelling's T2 were used to monitor the batch evolution process during the granulation and subsequent drying phase; moisture levels were predicted using a validated PLS model. Two data loggers were placed one near the bottom of the granulator bowl plenum where air enters the granulator and another inside the granulator in contact with the product in the fluid bed helped to monitor the humidity and temperature levels during the granulation and drying phase. The control charts were used for real time fault analysis, and were tested on normal batches and on three batches which deviated from normal processing conditions. This study demonstrated the use of NIRS and the use of humidity and temperature data loggers in conjunction with multivariate batch modeling as an effective tool in process understanding and fault determining method to effective process control in fluid bed granulation. [Copyright &y& Elsevier]

• The preparation of dripping pills was analyzed by a process analytical technology. • An image processing method was established to evaluate the dripping behaviors. • The algorithms for calculating the image indexes were designed. • The algorithm for grouping the dripping cycles was developed. • The image indexes could effectively represent the dripping pill weight fluctuation. The aim of this paper was to investigate the droplet morphology and evaluate the dripping behaviors during the dripping process based on image processing technology. An image acquisition system, which consisted of an industrial camera and a light source, was established. Four indexes including the area, the shape aspect ratio of the droplet, the shape parameter and the contact angle of the droplet images were studied to characterize the droplet morphology. The algorithms for calculating the image indexes and grouping the dripping cycles were designed. The relationships between the droplet morphology and the dripping behavior were conducted, such as the drop speed and the dripping pill weight. The method was well applied to Ginkgo biloba leaf dripping pills. The result showed that the variation trends of the area, the shape aspect ratio of the droplet and the contact angle could effectively characterize the droplet morphology and represent the dripping pill weight fluctuation. [ABSTRACT FROM AUTHOR]

Chromatography using polyamide column is one of the most critical purification operations that affect the safety and efficacy of traditional Chinese medicine ( TCM) products. To ensure successful operation and reduce time and solvent consumption, UV spectroscopy combined with multivariate data analysis as an online analytical tool was developed for monitoring the polyamide column chromatography of the TCM Danshen. The process trajectories were established by principal component analysis of the UV spectra and used to determine the endpoint of the washing stage and investigate the impacts of the process conditions. The online analysis method developed determined the concentration of salvianolic acid B (an important compound in Danshen) in the effluent rapidly and precisely with a coefficient of determination of 0.9963 and helped to collect salvianolic acid B quantitatively for determining the endpoint of elution. The methodology proposed is an effective approach applicable in guiding successful operations in the chromatographic separation. [ABSTRACT FROM AUTHOR]

Abstract: The Alisma rhizoma is widely used in the therapy of diabetes in traditional folk medicine of China. Compositional analysis of the alcohol extract of Alismatis Rhizoma (AEA) revealed that the eight compounds gotten from AEA are all belonging to protostane-type triterpenes. The AEA and compounds were incubated with 3T3‐L1 preadipocytes, glucose level in the 3T3‐L1 adipocytes culture medium and lipid content in 3T3‐L1 adipocytes were measured, and analysis of alpha-glucosidase inhibition of AEA and compounds. At the same time, the uptake of AEA by 3T3‐L1 adipocytes and the metabolism of AEA in SD rats were analyzed by HPLC-ESI/MS. As result, AEA increased glucose uptake in 3T3‐L1 adipocyte model, not increase adipogenesis; AEA inhibited alpha-glucosidase activity; alisol A-24-aceate (8) was absorbed by 3T3‐L1 adipocytes; and two compounds were detected in blood and three were detected in urine in SD rats. So AEA had protostane-type triterpenes, these type compounds in AEA may have hypoglycemic activity via inhibition of alpha-glucosidase activity and promotion of glucose uptake. In contrast to the anti-diabetic drug thiazolidinediones, they did not induce adipogenesis, avoiding the displeased effects of rosiglitazone. [Copyright &y& Elsevier]

Abstract: Alcohol precipitation is a critical unit operation during the manufacture of Chinese herbal injections. To facilitate enhanced process understanding and develop control strategy, the use of near-infrared spectroscopy (NIRS) combined with multivariate statistical process control (MSPC) methodology was investigated for in-line monitoring of alcohol precipitation. The effectiveness of the proposed approach was evaluated through an experimental campaign. Six batches were run under normal operating conditions to study batch-to-batch variation or batch reproducibility and establish MSPC control limits, while artificial process variations were purposefully introduced into the four test batches to assess the capability of the model for real-time fault detection. Several MSPC tools were compared and assessed. NIRS, in conjunction with MSPC, has proven to be a feasible process analytical technology (PAT) tool for monitoring batch evolution and potentially facilitating model-based advanced process control of the alcohol precipitation during the manufacture of Chinese herbal injections. [Copyright &y& Elsevier]

Abstract: A rapid method for simultaneous determination of main phenolic acids in Radix Salvia Miltrorrhiza extract solutions was developed using Fourier transform near infrared spectroscopy in transflective mode and multivariate calibration and HPLC-UV as the reference method. Partial least squares (PLS) algorithm was conducted on the calibration of regression models. The multiplicative scatter correction, Norris derivative and second derivative were adopted for the spectral pre-processing, and the number of PLS factors were optimized by leave-one-out cross-validation. The performance of the final model was evaluated according to root mean square error of prediction (RMSEP) and correlation coefficient (R). The R values achieved in the prediction set were above 0.93. The developed models were used for analysis of unknown samples and routine monitoring with satisfactory results. This work demonstrated that NIR spectroscopy combined with PLS algorithm could be used for the rapid determination of the main phenolic acids of Salvia Miltrorrhiza extract solutions. [Copyright &y& Elsevier]

Abstract: Entropy-based methods have been extensively used to measure the uncertainty information in a variety of fields. In this article, a novel information theory-based method for reducing noise of liquid chromatography–mass spectrometry (LC/MS) data was developed. The uncertainty existed in the LC/MS chromatograms was captured and evaluated by information entropy. By comparing the information entropy computationally derived from mass chromatograms, the good quality chromatograms and the noisy chromatograms can be distinguished. The proposed method was applied in processing LC/MS data of “Jing–Zhi–Guan–Xin” troche which is a well-known preparation of traditional Chinese medicine (TCM). The obtained result indicated that this method is beneficial to reduce noise of LC/MS data of complicated chemical samples, such as TCM. [Copyright &y& Elsevier]

Abstract: An effective, accurate and reliable method for the simultaneous separation and determination of eight active components (berberine, aloe-emodin, rhein, emodin, chrysophanol, baicalin, baicalein and wogonin) in Chinese medicine ‘YIQING’ capsule was developed using reverse phase high-performance liquid chromatography (RP-HPLC) coupled with diode array detection. The chromatographic separation was performed on a Lichrospher C18 column (250mm×4.6mm i.d. with 5.0μm particle size) with a simple linear gradient elution programme. Due to the different UV characteristic of these components, three detection wavelengths were utilized for the quantitative analysis (UV wavelength 254nm for anthraquinone derivatives, 278nm for flavones compounds, and 345nm for protoberberine alkaloids, respectively). Excellent linear behaviors over the investigated concentration ranges were observed with the values of R 2 higher than 0.99 for all the analytes. The recoveries, measured at three concentration levels, varied from 94.9% to 105.3%. The validated method was successfully applied to the simultaneously determination of these active components in ‘YIQING’ capsules from different production batches. [Copyright &y& Elsevier]

A novel self-learning expert system for diagnosis in Traditional Chinese medicine (TCM) was constructed by incorporating several data mining techniques, mainly including an improved hybrid Bayesian network learning algorithm, Naı¨ve–Bayes classifiers with a novel score-based strategy for feature selection and a method for mining constrained association rules. The data-driven nature distinguished the system from those existing TCM expert systems based on if-then rules to address knowledge elicitation problem. Moreover, the learned knowledge was provided in multiple forms including causal diagram, association rule and reasoning rules derived from classifiers. Finally, five representative cases were diagnosed to evaluate the performance of the system and the encouraging results were obtained. The results show that the prototype system performs well in diagnosis of TCM, and could be expected to be useful in the practice of TCM. [Copyright &y& Elsevier]

On-line monitoring and process control are the most efficient techniques to ensure high quality, low cost, and effective resource utilization in modern process engineering. The high-temperature and high-pressure operating conditions make the process control challenging during conversion reaction. In this study, the contents of main substances produced during chemical conversion of salvianolic acid A were monitored and controlled by an advanced process control method. At first, a kinetic model was established according to the reaction mechanism. Then, a high-precision partial least squares calibration model was established based on near-infrared spectroscopy. Finally, the conversion reaction was controlled in real-time by combining the data-driven model with the mechanism model. The correlation coefficients obtained by the data-driven model were all > 0.9. The fitting correlation coefficients of reaction rate constants were all > 0.9. The concentration of the reaction product was controlled within the limit by adjusting the reaction temperature based on the concentration-temperature curve. Combining the data-driven model with the mechanism model, the reaction process was controlled in real-time. This study emphasized the advantages of advanced process control for high temperature and high-pressure reaction processes and exemplified it as an important step in implementing intelligent production. [Display omitted] • Rapid and accurate monitoring of SAA conversion reaction using NIR. • Optimal reaction temperature was obtained. • Prediction of transformation substances based on kinetic model. • Combining the data-driven model with the mechanism model, the reaction process was controlled in real-time. [ABSTRACT FROM AUTHOR]

Objectives To investigate the feasibility of using near-infrared spectroscopy for rapid determination of main organic acids in Ginkgo biloba leaf extract (EGBL). Methods Main organic acids in EGBL were assayed using the HPLC method. Critical factors of the chromatographic separation were optimized by a novel analytical quality by design approach. Partial least squares-discriminant analysis (PLS-DA) was performed to screen the marker components, and principal component analysis (PCA) was utilized to distinguish the different samples. Then, spectral quantification potential was investigated using PLS and support vector machine (SVM) approaches. For modelling, different spectral preprocessing and wavelength selection methods were systematically compared. Key findings It was found that quinic acid, protocatechuic acid and 6-hydroxykynurenic acid were identified as possible index components. PLS-DA based on contents and PCA based on near-infrared spectra can both effectively distinguish the different EGBL samples. The calibration models with wonderful prediction performance can be both developed by the PLS and SVM algorithms. Conclusions NIR spectroscopy combined with chemometrics can realize the rapid and non-destructive qualitative and quantitative analysis of EGBL. The proposed method may be applied to quality control of EGBL and other natural products in commercial use. [ABSTRACT FROM AUTHOR]

Many biopharmaceutical manufacturers and researchers seek a comprehensive understanding and real-time monitoring of cell growth and metabolism to enhance the cell culture process. However, the biological complexity of cells and the intricacies of cell culture process have impeded the development of analytical and monitoring techniques. This study aims to present a complete picture of cell culture processes using in-line Raman spectroscopy. Initially, we proposed an efficient method for discriminating and removing anomalous spectra. Subsequently, Raman-based models for 27 components including amino acid, organic acid, lipid, organic alkali, alkaloid, alcohol, saccharide, biomass, physicochemical parameter, ion, and protein titer were established. The Q2 obtained by these models was greater than 0.8, and the relative percent difference (RPD) from external validation was greater than 2.0 except for glucose. Additionally, the proposed control charts effectively monitored normal batches and abnormal conditions such as bacterial contamination and insufficient feeding. In cases of unexplained culture abnormalities, the proposed workflow offered explanations. [Display omitted] • Monitoring and analysis of CHO cell culture processes using Raman spectroscopy. • Raman-based models of 27 different components in bioreactors were established. • Process trajectory of normal cultivation was described. • Abnormal cultivation was identified and explained. [ABSTRACT FROM AUTHOR]

This paper is to critically analyze the effects of solvent properties and composition on the solubility of trifloxystrobin. The solubility of trifloxystrobin in eight mono-solvents and two binary solvents was determined at temperatures ranging from 283.15 K to 318.15 K. Among the selected mono-solvents, the solubility of trifloxystrobin in alcohols was greater than that in alkanes and obeyed the following order: n-propanol > ethanol > methanol > 2-propanol > n-butanol > n-hexane > n-heptane > n-octane. For the binary solvents, as the mole fraction of good solvent (methanol/ethanol) increased, the solubility of trifloxystrobin increased monotonically at the set temperatures. In addition, the obtained solubility data was correlated with the Apelblat, NRTL, Wilson and Apelblat Jouyban Acree model, and these models were in good agreement with the experimental values. The NRTL model given the results of entropy, enthalpy and Gibbs free energy, which indicated that the dissolution was spontaneous, endothermic and entropically driven. The powder X-ray diffraction patterns proved that there was no polymorphic transformation during the solubility measurement. [ABSTRACT FROM AUTHOR]

A preparation process of salvianolic acid B (SAB) disodium salt from Salvia miltiorrhiza Bunge (Danshen) is provided in this work. A water extract quality standard was also developed to estimate the influences of Danshen quality on SAB disodium salt quality at an early stage of the preparation process. Crude SAB solution was obtained after water extraction, concentration, acidification, 1-butanol extraction, water washing, basification, and water back extraction. Extraction temperature, extraction pH, and back-extraction pH were identified to be key parameters for the preparation of crude SAB solution. These parameters were optimized with Box–Behnken designed experiments. Crude SAB solution was further purified with a chromatography process. AMBERCHROW CG161M resin was selected as the best adsorbent. SAB disodium salt could be obtained by drying the eluate. Considering the quality of Danshen may affect the purity and yield of SAB disodium salt, different batches of Danshen were used to prepare SAB disodium salt with the optimized parameters. Water extract indices of phenolic compound purity and phenolic compound yield were measured. By developing models between SAB disodium salt purity and yield with water extract indices, the quality standard of Danshen water extract was obtained. The application of water extract quality standards can improve the quality consistency of SAB disodium salt. The effects of different batches of Danshen raw materials on the final product could be evaluated at the beginning of production stages. The present method could prepare about five grams of high-purity SAB disodium salt (>95%) in one preparation cycle. The method reported in this work can also be used to develop process intermediate quality standards for other natural products. [ABSTRACT FROM AUTHOR]

A novel approach was developed to detect bed fluidity in gas–solid fluidized beds using diffuse reflectance near-infrared (NIR) spectroscopy. Because the flow dynamics of gas and solid phases are closely associated with the fluidization state, the fluidization quality can be evaluated through hydrodynamic characterization. In this study, the baseline level of NIR spectra was used to quantify the voidage of the fluidized bed. Two indicators derived from the NIR baseline fluctuation profiles were investigated to characterize bed fluidity, named bubble proportion and skewness. To establish a robust fluidity evaluation method, the relationships between the indicators and bed fluidity were investigated under different conditions firstly, including static bed height and average particle size. Then, a generalized threshold was identified to distinguish poor and good bed fluidity, ensuring that the probability of the α- and β-errors was less than 15% regardless of material conditions. The results show that both indicators were sensitive to changes in bed fluidity under the investigated conditions. The indicator of skewness was qualified to detect bed fluidity under varied conditions with a robust threshold of 1.20. Furthermore, the developed NIR method was successfully applied to monitor bed fluidity and for early warning of defluidization in a laboratory-scale fluidized bed granulation process. [ABSTRACT FROM AUTHOR]

Dammarane-type saponins (DTSs) exist in various medicinal plants, which are a class of active ingredients with effects on improving myocardial ischemia and immunomodulation. In this study, a quantitative 1H NMR method of total DTSs in herbal medicines was developed based on the analytical procedure lifecycle. In the first stage (analytical procedure design), the Ishikawa diagram and failure mode effects and criticality analysis were used to conduct risk identification and risk ranking. Plackett–Burman design and central composite design were used to screen and optimize critical analytical procedure parameter. Then, the method operable design region was obtained through modeling. In the second stage (analytical procedure performance qualification), the performance of methodological indexes was investigated based on analytical quality by design. As examples of continued procedure performance verification, the method was successfully applied to determine the total DTSs in herbal pharmaceutical preparations and botanical extracts. As a general analytical method to quantify total DTSs in medicinal plants or pharmaceutical preparations, the developed method provides a new quality control strategy for various products containing dammarane-type saponin. [ABSTRACT FROM AUTHOR]

The aim of this study was to present a novel analytical quality by design (AQbD) approach for developing an HPLC method to analyze herbal extracts. In this approach, critical method attributes (CMAs) and critical method parameters (CMPs) of the analytical method were determined using the same data collected from screening experiments. The HPLC-ELSD method for separation and quantification of sugars in Codonopsis Radix extract (CRE) samples and Astragali Radix extract (ARE) samples was developed as an example method with a novel AQbD approach. Potential CMAs and potential CMPs were found with Analytical Target Profile. After the screening experiments, the retention time of the D-glucose peak of CRE samples, the signal-to-noise ratio of the D-glucose peak of CRE samples, and retention time of the sucrose peak in ARE samples were considered CMAs. The initial and final composition of the mobile phase, flow rate, and column temperature were found to be CMPs using a standard partial regression coefficient method. The probability-based design space was calculated using a Monte-Carlo simulation method and verified by experiments. The optimized method was validated to be accurate and precise, and then it was applied in the analysis of CRE and ARE samples. The present AQbD approach is efficient and suitable for analysis objects with complex compositions. [ABSTRACT FROM AUTHOR]

The present work reports developing the first process analytical technology (PAT)-based real-time feedback control system for maintaining the Ginkgo biloba leaf dripping pills weight during manufacturing. The opening degree of the drop valve and the weight of dripping pills were chosen as the manipulated variable and as the controlled variable, respectively. A proportional-integral controller was programmed to automatically reach the desired dripping pills weight by adjusting the opening degree of the drop valve. The closed-loop feedback control system could automatically compensate for the disturbances and ensure a predefined weight of the dripping pills with excellent robustness, high accuracy, and high efficiency during manufacturing. Furthermore, the closed-loop feedback control system improved the process capability of the dripping process, and the process capability index was > 1.67. This study provides a new approach to real-time control of the weight of dripping pills and improves the process capability during Ginkgo biloba leaf dripping pills manufacturing. [ABSTRACT FROM AUTHOR]

E'Jiao is a traditional Chinese medicine derived from donkey skin. E'Jiao is reported to suppress elevated bone remodelling in ovariectomised rats but its mechanism of action is not known. To bridge this research gap, the current study aims to investigate the effects of E'Jiao on skeletal mineralisation, osteocyte and WNT signalling inhibitors in ovariectomised rats. Female Sprague–Dawley rats (3 months old) were ovariectomised and supplemented with E'Jiao at 0.26 g/kg, 0.53 g/kg and 1.06 g/kg, or 1% calcium carbonate (w/v) in drinking water. The rats were euthanised after two months of supplementation and their bones were collected for Fourier-transform infrared spectroscopy, histomorphometry and protein analysis. Neither ovariectomy nor treatment affected the skeletal mineral/matrix ratio, osteocyte number, empty lacunar number, and Dickkopf-1 and sclerostin protein levels (p > 0.05). Rats treated with calcium carbonate had a higher Dickkopf-1 level than baseline (p = 0.002) and E'Jiao at 0.53 g/kg (p = 0.002). In conclusion, E'Jiao has no significant effect on skeletal mineralisation, osteocyte and WNT signalling inhibitors in ovariectomised rats. The skeletal effect of E'Jiao might not be mediated through osteocytes. [ABSTRACT FROM AUTHOR]

A novel quantitative 1H NMR (Q-NMR) combined with HPLC-MS method has been proposed for investigating the degradation process of traditional Chinese medicine (TCM) components. Through this method, in-situ monitoring of dynamics degradation process of lithospermic acid (LA), one of the popular polyphenolic acids in TCM, was realized under low oxygen condition. Additionally, this methodology was proved to be simple, rapid and specific. Degradation kinetic runs have been carried out to systematically investigate the effects of two key environmental factors, initial pH values and temperatures. Eight main degradation products of LA were detected, seven of which were tentatively structural elucidated with the help of both NMR and LC-MS in this work and salvianolic acid A (Sal A) was the primary degradation product of LA. A possible degradation pathway of LA was proposed, subsequently. The results showed that the degradation of LA followed pseudo-first-order kinetics. The apparent degradation kinetic constants increased as the initial pH value of the phosphate buffer increased. Under the given conditions, the rate constants of overall degradation as a function of temperature obeyed the Arrhenius equation. Our results proved that the Q-NMR combined with HPLC-MS method can be one of the most promising techniques for investigating degradation process of active components in TCM. [ABSTRACT FROM AUTHOR]

Background: Xiaochaihu capsule is composed of seven traditional Chinese medicines. The pharmacopoeia only focuses on the quantitative detection of baicalin, which cannot fully reflect the quality of the preparation. Some medium polar components were used to establish the fingerprint of Xiaochaihu capsule, but there was no report on the strong polar components. Methods: A high performance liquid chromatography-corona charged aerosol detection technology was used to establish a fingerprint analysis method for Xiaochaihu capsules following an analytical quality by design approach. Definitive screening designed experiments were used to optimize the method parameters. A stepwise regression method was used to build quantitative models. The method operable design region was calculated using the experimental error simulation method. Plackett–Burman designed experiments were carried out to test robustness. Results: The contents of four components were simultaneously determined. There were seven common peaks in the fingerprint. The common peak area accounted for 91.72%. Both fingerprint and quantitative analysis methods were validated as applicable in the methodology study. The quantitative fingerprint analysis method for sugar components can fill the gap in the detection of strong polar components in the existing methods. It provides a new technology for the comprehensive overall evaluation of Xiaochaihu capsule. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop and validate a near-infrared (NIR) spectroscopy based method for in-line quantification during the second alcohol precipitation process of Astragali radix. In total, 22 calibration experiments were carefully arranged using a Box–Behnken design. Variations in the raw materials, critical process parameters, and environmental temperature were all included in the experimental design. Two independent validation sets were built for method evaluation. Validation set 1 was used for optimization. Different spectral pretreatments were compared using a "trial-and-error" approach. To reduce the calculation times, the full-factorial design was applied to determine the potential optimal combinations. Then, the best parameters for the pretreatment algorithms were compared and selected. Partial least squares (PLS) regression models were obtained with low complexity and good predictive performance. Validation set 2 was used for a thorough validation of the NIR spectroscopy method. Based on the same validation set, traditional chemometric validation and validation using accuracy profiles were conducted and compared. Conventional chemometric parameters were used to obtain the overall predictive capability of the established models; however, these parameters were insufficient for pharmaceutical regulatory requirements. Then, the method was fully validated according to the ICH Q2(R1) guideline and using the accuracy profile approach, which enabled visual and reliable representation of the future performances of the analytical method. The developed method was able to determine content ranges of 8.44–39.8% at 0.541–2.26 mg/mL, 0.118–0.502 mg/mL, 0.220–0.940 mg/mL, 0.106–0.167 mg/mL, 0.484–0.879 mg/mL, and 0.137–0.320 mg/mL for total solid, calycosin glucoside, formononetin glucoside, 9, 10-dimethoxypterocarpan glucopyranoside, 2′-dihydroxy -3′, 4′-dimethoxyisoflavan glucopyranoside, astragloside II, and astragloside IV, respectively. These ranges were specific to the early and middle stages of the second alcohol precipitation process. The method was confirmed to be capable of achieving an in-line prediction with a very acceptable accuracy. The present study demonstrates that accuracy profiles offer a potential approach for the standardization of NIR spectroscopy method validation for traditional Chinese medicines (TCMs). [ABSTRACT FROM AUTHOR]

Process analysis and monitoring during the manufacturing of the dripping pills are essential. However, research on developing sensor‐based technology or process analytical technology (PAT) tools to analyze and monitor the dripping process is minimal. The purpose of this work is to develop a fast and non‐destructive laser detection system for quantitative visualization of droplets, which involves detecting the size of the droplet and calculating the weight of the dripping pills during the dripping process. Several factors influencing the detection performance of the detection system and the detection system capability for quantitation of the pill weight were explored. The laser detection system accurately detects the weight of the dripping pills with the coefficients of determination (R2) higher than 0.99. It was also robust concerning the variation in critical process parameters and critical material attributes. Furthermore, the laser detection system was successfully applied to the production line of Ginkgo biloba leaf dripping pills to monitor the dripping pills weight. The proposed laser detection system can analyze and monitor the dripping process in dripping pill manufacturing with stable performance, high accuracy, and high efficiency. [ABSTRACT FROM AUTHOR]

A near infrared (NIR) spectroscopy-based method was developed for monitoring the hydrolysis process of bear bile powder. During the hydrolysis process, samples were collected and measured using both NIR spectrometer and high performance liquid chromatography. The quantitative calibration models were established with the collected NIR spectra and the reference concentrations of tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), ursodeoxycholic acid (UDCA), and chenodeoxycholic acid (CDCA) using partial least squares regression algorithm. After the models were established and validated, the samples of new batches can be determined rapidly, and the hydrolysis process of bear bile powder can be monitored quantitatively. Additionally, a moving block of standard deviation (MBSD) method was also developed for the endpoint determination of the hydrolysis process. The proposed methods have reduced the laborious workload of process sample analysis significantly, and the fast analytical results have contributed to the understanding and controlling of the bear bile powder hydrolysis process. [ABSTRACT FROM AUTHOR]

Direct analysis in real time mass spectrometry (DART-MS) provides a new analytical method for traditional Chinese medicine (TCM). The present study investigated the effects of key ion source operating parameters on DART-MS analysis of various TCM active components. A total of 18 active components, including phenylpropanoids, alkaloids, saponins, flavones, volatile oils, and glycosides, were examined. For each substance, the peak area and signal-to-noise of its characteristic ions under different reagent gases and heater temperatures were compared. Based on the comparison, the relationships among chemical structures, ion source parameters and instrument responses were revealed. Finally, some suggestions about choosing reagent gas and heater temperature were proposed for types of TCM active substance, which offered a reference for the application of DART-MS on TCM analysis. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to establish a rapid and comprehensive method for quantitative determination of complex ingredients in Traditional Chinese Medicine injections. Methods A 1H quantitative nuclear magnetic resonance method was developed to simultaneously quantify comprehensive chemical components in Danshen Injection. Multivariate statistical analysis technique was applied to quality evaluation of multiple batches of Danshen injection. Key findings A complete signal attribution to the 1H nuclear magnetic resonance spectrum of Danshen injection was developed and performed for the first time. A total of 32 chemical components were identified from Danshen Injection. Among them, 20 were quantified simultaneously, accounting for up to 80% (w/w) of the total solids and 95% (w/w) of total organic matter, representing success compared to the previous studies. The developed method was further applied to analyze 13 batches of Danshen Injection from three manufacturers to make a realistic analysis. Conclusion It was found that the comprehensive chemical information provides an adequate characterization for quality profiles among different commercial batches of Danshen Injection. The developed method further offered a guarantee for improving the consistency and safety of Traditional Chinese Medicine injections. [ABSTRACT FROM AUTHOR]

This paper proposed an approach to predict the breakthrough curves for herbal medicine adsorption. The saponins adsorption process was taken as an example. The Yoon-Nelson model was used to fit the breakthrough curves of saponins and the model parameters in different batches were obtained. The model parameters were correlated with saponin concentrations in loading solution and flow rate using polynomial regression models. According to the polynomial regression models, the breakthrough curves could be predicted and the optimal adsorption end-point could be calculated early-on. This research provided a new method for predicting the end-points of the adsorption process of herbal extracts. [ABSTRACT FROM AUTHOR]

Ethanol precipitation is an important purification process affecting the safety and efficacy of botanical injections. In this paper, the second ethanol precipitation of Guanxinning injection was optimized with response surface methodology as a sample to represent the principles of indicator selection. The influences of three factors, including dry matter content of concentrated supernatant (DMCCS), refrigeration temperature, and the mass ratio of ethanol and concentrated supernatant (E/CS ratio) were explained based on the precipitation mechanism. To characterize the effects of ethanol precipitation on drug safety, drug efficacy, and drug quality control, phenolic compound recovery and dry matter removal were selected as optimization criteria. In the optimization, E/CS ratio was set to 3.60. The optimum operating conditions were found at refrigeration temperature of 18.66°C and DMCCS of 0.58. Most of the experimental results at optimum operating conditions agreed well with the predicted results. [ABSTRACT FROM AUTHOR]

Highlights: [•] Q-NMR method to determine Sal B as well as its degradation products is described. [•] The method is applied to monitor the hydrolysis of Sal B in low oxygen condition. [•] The concentration results are fitted to a kinetic model to obtain rate constants. [•] Q-NMR method is proved to be suitable and effective for degradation study. [ABSTRACT FROM AUTHOR]

Highlights: [•] The adsorption efficiencies at the end of the process were predicted early-on. [•] Process parameters were adjusted according to the raw materials variation. [•] The strategy can lead the process towards the target adsorption efficiencies. [Copyright &y& Elsevier]

[Display omitted] Droplets find wide application across diverse industries, where maintaining their quality is paramount. Precise control over the substance content within droplets demands non-destructive and online analysis techniques, such as Process Analytical Technology (PAT), often integrated with control strategies. In this context, the present study focuses on the example of controlling droplet quality during the dripping process of pills. Leveraging the dripping and image acquisition systems established in previous research, a novel feedback control system centered on image processing was devised for the quality control of dripping pills. The system was developed and its efficacy was assessed, yielding satisfactory outcomes. The proposed system facilitates real-time monitoring of pill weight through the analysis of droplet images during the dripping process, thereby offering real-time feedback control of pill weight. Importantly, this system holds potential for broader applications beyond the scope of this study. [ABSTRACT FROM AUTHOR]

Alcohol precipitation (AP) is a common method to achieve separation and purification in the process of food and herbal preparations. The response surface methodology (RSM) was applied to study and optimize the AP of Danshen, regarding the recovery of danshensu (RD) and the removal of saccharides (RS). A fractional factorial design was initially performed and solid content, ethanol consumption, acid consumption, and temperature showed significant influence on RD and RS. A Box-Behnken design with 28 experimental runs was then applied and two polynomial equations were established, based on which the effects of significant factors and their interactions were discussed. The optimum operating conditions were solid content at 66.0%, ethanol consumption at 4.3 mL/g, acid consumption at 0 g/g, and temperature at 10.7°C. The average experimental RD and RS under the optimum conditions were obtained to be 66.25 ± 1.01% and 61.64 ± 1.84%, respectively, which agreed well with the predicted values (68.85% for RD and 61.92% for RS). [ABSTRACT FROM AUTHOR]

Abstract: Traditional Chinese medicine (TCM) products are usually manufactured through batch processes. To improve batch-to-batch reproducibility, the feasible approaches for real-time monitoring of batch evolution need to be developed. In-line near-infrared (NIR) spectroscopy combined with multivariate data analysis as an efficient process analytical technology (PAT) tool, is presented in this study for real-time batch process monitoring. Liquid–liquid extraction is a widely used purification technology in the TCM manufacture, and selected as the example to demonstrate the effectiveness of this PAT tool. Multi-way partial least squares (MPLS) model was developed based on in-line measured NIR spectral data of ten normal operation condition (NOC) batches. Three kinds of multivariate control charts (scores, Hotelling T 2 and DModX) were used to monitor the evolution of six test batches with artificial batch variations, including the change of starting material quality attributes and abnormal operation conditions. The approach was found very effective for real-time monitoring of process deviations from NOC batches. It is an alternative promising tool for monitoring batch reproducibility of the unit operations during the manufacture of TCM. [Copyright &y& Elsevier]

Abstract: There is a lack of methods to analyze large numbers of traditional Chinese medicine (TCM) samples quickly and efficiently. Here we present a near infrared (NIR) spectroscopy-based method for the rapid analysis of Honeysuckle extracts. NIR spectra of 124 Honeysuckle extract samples produced within a four-year period were collected in the diffuse reflection mode and pretreated with multiplicative scatter correction (MSC), smoothing and derivative. Using partial least squares regression (PLSR), including PLS1 and PLS2, we established and validated the calibration models of six organic acids. Our results showed that both accuracy and precision of the NIR spectroscopy-based method meet the requirements of a traditional Chinese medicine (TCM) factory. This new method has the potential to save time, efforts and cost associated with the analysis of large quantities of unknown samples and will be particularly applicable to TCM factories for cost reduction. [Copyright &y& Elsevier]

Abstract: A novel and high throughput chemiluminescence (CL) method for determination of chemical oxygen demand (COD) in water sample was originally developed based on potassium permanganate–glutaraldehyde CL system. With this method, dissolved organic matter in water samples was digested by excess acid potassium permanganate, the reacted mixture solutions containing surplus KMnO4 were added in wells of a 96-well plate, followed by injection of glutaraldehyde in the wells, and CL was then produced along with the reaction of the added glutaraldehyde with the surplus KMnO4 and detected by a photomultiplier tube (PMT). The difference (ΔI) between the CL intensity for distilled water and that for sample water was proportional to the COD value of water sample. The calibration graph was linear in the range of 0.16–19.24mgL−1 with a detection limit of 0.1mgL−1. A complete analysis could be performed in 40min including digestion and detection, giving a very high throughput of 3×96 samples in about 60min. Compared with the conventional methods, this method is simple and sensitive and consumes very limited and cheap reagents. Owing to its rapid, automatic, high throughput and low cost characteristics, the presented CL method has been applied successfully to the determination of COD in real water samples (n =32) with satisfactory results. [Copyright &y& Elsevier]

Rationale: Kaixin San (KXS) is a prescription traditional Chinese medicine (TCM) with the effects of “tonifying the kidney and brain” and “improving memory”. The volatile organic compounds (VOCs) in KXS could effectively improve senile dementia and depression, but only few studies have focused on the overall characterization of VOCs in KXS and the quantitative study of the main active components. Methods: We have developed a strategy to correlate the results from headspace gas chromatography/ion mobility spectrometry (HS‐GC/IMS) and headspace gas chromatography/mass spectrometry (HS‐GC/MS) for the comprehensive characterization of VOCs in KXS and the quantitative analysis of the main pharmacodynamic substances. Results: A totsal of 68 low molecular weight VOCs were identified in KXS by HS‐GC/IMS at room temperature and atmospheric pressure; 117 VOCs were identified and 10 components (isocalamenediol, α‐asarone, β‐asarone, methyl eugenol, isoeugenol methyl ether, camphor, anethol, 2,4‐di‐tert‐butylphol, linalool, asarylaldehyde) as the quality markers of KXS based on HS‐GC/MS. Conclusions: This results from this study provide a foundation for quality control, pharmacodynamic mechanism research and further development of KXS, and provides more convincing data supporting the VOCs of other natural products. [ABSTRACT FROM AUTHOR]

• NMR can track detailed potential chemical markers of ethanol precipitation process. • The quality consistency of process intermediates was evaluated by PCA. • MLR was applied to study the transfer laws of the 16 potential chemical markers through statistical modeling. • Typical markers of ethanol precipitation process included phenolic acids, saccharides, amino and organic acids. Process quality control of the herbal medicines (HMs) still hits technical bottlenecks due to their complicated multi-step pretreating. Nuclear magnetic resonance (NMR) spectroscopy could serve as a powerful technique able to obtain comprehensive information of chemical compounds in the manufacturing process of HMs by a single analytical test. In this study, ethanol precipitation, a critical pretreating process of an especially widely used HM preparation, was conducted with different process variables, including ethanol-material ratio, apparent ethanol concentration and moisture concentration of the raw material, 40 lab-scale experiments of ethanol precipitation were orchestrated by a full factor design with additional central composite circumscribed experiments. Then, 16 metabolites were recognized as the most critical potential chemical markers in the process by 1H NMR spectra and orthogonal partial least squares-discriminant analysis (OPLS-DA). Finally, multiple linear regression (MLR) was applied to evaluate the impacts of process variables and their interaction on the chemical markers and explain the consistency variation of the process intermediates. The results promote the further understanding of ethanol precipitation process and open up possibilities to develop a more effective process quality control methodology of an HM, through providing a more in-depth and improved pharmaceutical process understanding and characterization. [ABSTRACT FROM AUTHOR]