A New Evaluation Metric for Quantitative Accuracy of LC-MS/MS-Based Proteomics with Data-Independent Acquisition.

Data-independent acquisition (DIA) has improved the identification and quantitation coverage of peptides and proteins in liquid chromatography-tandem mass spectrometry-based proteomics. However, different DIA data-processing tools can produce very different identification and quantitation results for the same data set. Currently, benchmarking studies of DIA tools are predominantly focused on comparing the identification results, while the quantitative accuracy of DIA measurements is acknowledged to be important but insufficiently investigated, and the absence of suitable metrics for comparing quantitative accuracy is one of the reasons.

Simultaneous quantification of six proteins related to liver injury using nano liquid chromatography-tandem mass spectrometry.

Rationale: In clinical diagnosis of liver injury, which is an important health concern, serum aminotransferase assays have been the go-to method used worldwide. However, the measurement of serum enzyme activity has limitations, including inadequate disease specificity and enzyme specificity.

Methods: With the high selectivity and specificity provided by nano liquid chromatography-tandem mass spectrometry (LC/MS/MS), this work describes a method for the simultaneous determination of six proteins in liver that can be potentially used as biomarkers for liver injury: glutamic-pyruvic transaminase 1 (GPT1), glutamic oxaloacetic transaminase 1 (GOT1), methionine adenosyl transferase 1A (MAT1A), glutathione peroxidase 1 (GPX1), cytokeratin 18 (KRT18) and apolipoprotein E (APOE).

Data-Driven Tool for Cross-Run Ion Selection and Peak-Picking in Quantitative Proteomics with Data-Independent Acquisition LC-MS/MS.

Proteomics provides molecular bases of biology and disease, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a platform widely used for bottom-up proteomics. Data-independent acquisition (DIA) improves the run-to-run reproducibility of LC-MS/MS in proteomics research. However, the existing DIA data processing tools sometimes produce large deviations from true values for the peptides and proteins in quantification.

An integrated strategy of spectrum-effect relationship and near-infrared spectroscopy rapid evaluation based on back propagation neural network for quality control of Paeoniae Radix Alba.

The quantitative analysis of near-infrared spectroscopy in traditional Chinese medicine has still deficiencies in the selection of the measured indexes. Then Paeoniae Radix Alba is one of the famous "Eight Flavors of Zhejiang" herbs, however, it lacks the pharmacodynamic support, and cannot reflect the quality of Paeoniae Radix Alba accurately and reasonably. In this study, the spectrum-effect relationship of the anti-inflammatory activity of Paeoniae Radix Alba was established.

Capillary electrophoresis-mass spectrometry analysis of bisphenol A and its analogues in bottled tea beverages with dynamic pH focusing.

A simple and sensitive method for the determination of bisphenol A and its analogues at the ng/mL level in bottled tea beverages is presented. This method utilized a dynamic pH junction to focus the analyte into a more concentrated zone, based on the electrophoretic mobility difference of analytes in the sample matrix and background electrolytes in capillary electrophoresis coupled to mass spectrometry (CE-MS). The optimised analyte focusing led to enhanced signal detection with average peak heights for five bisphenols of 53-170 folds higher than conventional injections.

Single Standard Substance for the Simultaneous Determination of Eleven Components in the Extract of Paeoniae Radix Alba (Root of Pall.).

Paeoniae Radix Alba (PRA), an herbal drug produced from the root of Pall., is widely used in many herbal medicine prescriptions/preparations. Since the pharmacological effects of PRA come from multiple chemical components, it is important to establish a method for the determination of those components in PRA extracts with simple operation and low cost, which is more suitable to evaluate the quality of PRA extracts and optimize the extraction process.

Data-driven development of liquid chromatography-mass spectrometry methods for combined sample matrices.

Herbal medicine formulas (HMFs), the combinations of two or more herbal medicine (HM) ingredients required in a single prescription, are a typical kind of combined sample matrices. LC-MS is a powerful platform for the analyses of such complex samples. The optimization of separation conditions may require a lot of experiments, because multiple analytes need to be separated from a plethora of possible interfering compounds in the sample mixture containing different herbal medicines.

The Application of Chemometrics for Efficiency Enhancement and Toxicity Reduction in Cancer Treatment with Combined Therapy.

Chemometrics is an important emerging discipline with unique charm formed by the intersection of mathematics, statistics, chemistry and computer science. The application of chemometrics in the field of pharmacy has injected fresh blood into the scientific research and clinical practice of medicine and has provided a sufficient scientific basis for drug analysis and content determination to solve the problem of cancer treatment with combined therapy in different ranges. This paper introduces the basic principles, advantages and disadvantages of several commonly used pattern recognition and multidimensional correction methods of chemometrics, reviews the application of chemometrics for efficiency enhancement and toxicity reduction in cancer treatment with combined therapy and summarizes its development and prospects in the future.

Enantioselective analysis in complex matrices using capillary electrophoresis-mass spectrometry: A case study of the botanical drug Corydalis Rhizoma.

Enantioselective analysis is critically important in the pharmaceutical and agricultural industries. However, most of the methods reported were developed for the analysis of pure racemates acquired from chemical synthesis or purification. Direct analysis of chiral enantiomers in complex matrices has rarely been reported.

Development and validation of in-line near-infrared spectroscopy based analytical method for commercial production of a botanical drug product.

Near-infrared (NIR) spectroscopy is one of the most successful pharmaceutical process analytical tools. For botanical drug products (BDPs), many studies have applied NIR spectroscopy for rapid analysis of botanical raw materials, extracts and formulations. However, the real-time process analysis reported for BDPs was still mainly conducted on lab- or pilot- scale equipment, where some essential conditions of the materials and process parameters can be easily controlled for NIR spectral measurement.

[Medication regularities of traditional Chinese medicine formulas for six kinds of pains by data-mining approach].

To study and compare the medication regularities of traditional Chinese medicine formulas(TCMFs) for the six kinds of pains,namely abdominal pain,headache,epigastric pain,hypochondriac pain,heartache and backache,using a data-mining approach,in order to provide reference for relevant studies for the compatibility mechanism and new compound development of related TCMFs. A total of 2 443 TCMFs for pains were collected from the Dictionary of Chinese Medicine Prescriptions,and analyzed using the Apriori algorithm based on three indicators,namely confidence,lift and support,so as to study pivotal traditional Chinese medicines(TCMs) for each pain and their compatibility regularities. The results showed that deficiency tonifying medicines(such as Glycyrrhizae Radix et Rhizoma and Angelicae Sinensis Radix),Qi-regulating medicines(like Aucklandiae Radix) and blood circulation promoting medicines(like Chuanxiong Rhizoma) were commonly used TCMs for pains.

Advancement in the chemical analysis of Paeoniae Radix (Shaoyao).

Paeoniae Radix Alba (baishao or white peony root) and Paeoniae Radix Rubra (chishao or red peony root) are two highly valuable traditional Chinese medicines (TCMs) usually indicated for painful conditions, menstrual disorders and viral infections. These two TCMs are collectively referred to as shaoyao (Paeoniae Radix) due to their close origins and similar chemical compositions. Modern research indicates that monoterpene glycosides, polyphenols and paeonols are the three main types of compounds related to the pharmacological activities of Paeoniae Radix.

Rapid HPLC Analytical Method Development for Herbal Medicine Formulae Based on Retention Rules Acquired from the Constituting Herbs.

Herbal medicine (HM) formulae are the combinations of two or more types of constituting herbs. This study has proposed a novel approach to efficiently develop HPLC methods for HM formulae, which take advantage of the mutual retention rules between HM formulae and their constituting herbs. An HM formula composed of two herbs, Radix Salviae Miltiorrhizae and Rhizoma Chuanxiong, was taken as a case study.

[Rapid determination of nine components in the first extraction process of Xingnaojing injection by using ultraviolet spectroscopy].

In this study, an analytical method based on ultraviolet spectroscopy was established for the rapid determination of nine components including isophorone, 4-methylene-isophorone, curcumenone, curcumenol, curdione, curzerenone, furanodienone, curcumol and germacrone in the first extraction process of Xingnaojing injection. 166 distillate samples of Gardeniae Fructus and Radix Curcumae were collected in the first extraction process of Xingnaojing injection. The ultraviolet spectra of these samples were collected, and the contents of the nine components in these samples were determined by high performance liquid chromatography.

Single standard substance for the determination of nine volatile components in the distillate of Fructus Gardeniae and Radix Curcumae (an intermediate of Xingnaojing Injection).

Xingnaojing Injection is a traditional Chinese medicine extensively used for stroke and cerebral ischemia. For better in-process quality control of Xingnaojing Injection, a method for the analysis of its intermediate (i.e.

Statistical Model Based HPLC Analytical Method Adjustment Strategy to Adapt to Different Sets of Analytes in Complicated Samples.

Introduction: On account of the complicated compositions of the products like traditional Chinese medicines (TCMs) and functional foods, it is a common practice to determine different sets of analytes in the same product for different purposes.

Objective: To efficiently develop the corresponding HPLC methods, a statistical model based analytical method adjustment (SMB-AMA) strategy was proposed.

Methods: In this strategy, the HPLC data acquired with design of experiments methodology were efficiently utilised to build the retention models for all the analytes and interferences shown in the chromatograms with multivariate statistical modelling methods.

Root Cause Analysis of Quality Defects Using HPLC-MS Fingerprint Knowledgebase for Batch-to-batch Quality Control of Herbal Drugs.

Introduction: The batch-to-batch quality consistency of herbal drugs has always been an important issue.

Objectives: To propose a methodology for batch-to-batch quality control based on HPLC-MS fingerprints and process knowledgebase.

Methods: The extraction process of Compound E-jiao Oral Liquid was taken as a case study.

Rapid process development of chromatographic process using direct analysis in real time mass spectrometry as a process analytical technology tool.

The concept of quality by design (QbD) is widely applied in the process development of pharmaceuticals. However, the additional cost and time have caused some resistance about QbD implementation. To show a possible solution, this work proposed a rapid process development method, which used direct analysis in real time mass spectrometry (DART-MS) as a process analytical technology (PAT) tool for studying the chromatographic process of Ginkgo biloba L.

An approach to optimize the batch mixing process for improving the quality consistency of the products made from traditional Chinese medicines.

The efficacy of traditional Chinese medicine (TCM) is based on the combined effects of its constituents. Variation in chemical composition between batches of TCM has always been the deterring factor in achieving consistency in efficacy. The batch mixing process can significantly reduce the batch-to-batch quality variation in TCM extracts by mixing them in a well-designed proportion.

Quality by design for herbal drugs: a feedforward control strategy and an approach to define the acceptable ranges of critical quality attributes.

Introduction: The concept of quality by design (QbD) has been widely accepted and applied in the pharmaceutical manufacturing industry. There are still two key issues to be addressed in the implementation of QbD for herbal drugs. The first issue is the quality variation of herbal raw materials and the second issue is the difficulty in defining the acceptable ranges of critical quality attributes (CQAs).

[Application of ultraviolet spectroscopy for rapid analysis in extraction process of danhong injection].

In this work, a rapid analysis method basing on ultraviolet spectroscopy was established for the determination of danshensu, protocatechuic aldehyde, rosmarinci acid, lithospermic acid and salvianolic acid B in the extraction process of Danhong injection. In the extraction process of Danshen and Honghua crude drugs, 44 extraction solution samples were collected and the contents of the five components were determined by HPLC analysis. The ultraviolet spectra of the samples were collected.

[An approach to determine critical process parameters for ethanol precipitation process of danhong injection].

Objective: To establish a method integrating multi-targets for determining critical process parameters of the manufacturing process of traditional Chinese medicine.

Method: The ethanol precipitation process of Danhong injection was taken as an application case of the method established. Fractional factorial design of experiments were conducted.

[Feedforward control strategy and its application in quality improvement of ethanol precipitation process of danhong injection].

In this work, a feedforward control strategy basing on the concept of quality by design was established for the manufacturing process of traditional Chinese medicine to reduce the impact of the quality variation of raw materials on drug. In the research, the ethanol precipitation process of Danhong injection was taken as an application case of the method established. Box-Behnken design of experiments was conducted.

Multivariate data analysis of UV spectra in monitoring elution and determining endpoint of chromatography using polyamide column.

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.

Application of quality by design to the process development of botanical drug products: a case study.

This paper was designed to assess the value of quality by design (QbD) to improve the manufacturing process understanding of botanical drug products. Ethanol precipitation, a widely used unit operation in the manufacture of botanical drug products was employed to illustrate the use of QbD, taking the process of danshen (the dry root of Salvia miltiorrhiza Bunge) as an example. The recovery of four active pharmaceutical ingredients (APIs) and the removal of saccharides were used to represent the performance of ethanol precipitation.