Quality Control Of Drugs Research Articles

Advances in heparin structural analysis by chromatography technologies

Heparin （Hp） is the most widely used anticoagulant drug in the clinics， with an annual global output of over 10 billion dollars. Hp， a member of the glycosaminoglycans （GAGs）， is prepared from porcine intestinal mucosa via extraction， separation， and purification. Hp is a linear polysaccharide with repeating disaccharide units. Low-molecular-weight heparins （LMWHs） are depolymerized from Hp via chemical or enzymatic degradation. Compared with Hp， LMWHs exhibit less bleeding side effect， milder immunogenicity， and higher bioavailability when injected subcutaneously. In general， Hps， including LMWHs， are high complex drugs with large molecular weights （MWs）， inhomogeneous MW distributions， and structural heterogeneity， including different degrees and locations of sulfonation， and unique residues generated from different production processes. Thus， developing efficient analytical methods to elucidate the structures of Hps and characterize or quantitate their properties is extremely challenging. Unfortunately， this problem limits their quality control， production optimization， clinical safety monitoring， and new applications. Research has constantly sought to elucidate the complicated structures of Hp drugs. Among the structural analysis and quality control methods of Hp currently available， chromatographic methods are the most widely studied and used. However， no literature thoroughly summarizes the specific applications of chromatographic methods in the structural analysis， manufacturing process， and quality control of Hp drugs. This paper systematically organizes and describes recent research progresses of the chromatographic methods used to analyze Hp drugs， including the identification and composition of monosaccharides， disaccharides， oligosaccharides， and polysaccharides. The applications， innovations， and limitations of these chromatographic methods are also summarized in this review. The insights obtained in this study will help production and quality control personnel， as well as drug researchers， obtain a deeper understanding of the complex structures of Hp drugs. This paper also provides a comprehensive reference for the structural analysis and quality control of Hps， proposes ideas for the development of new quality control methods， and lays a strong foundation for the in-depth structural elucidation of Hp drugs.

Prevalence of Poor Quality Ciprofloxacin and Metronidazole Tablets in Three Cities in Cameroon.

Quality is one of the essential components of medicines and needs to be ensured to preserve the population's health. This can be achieved through post-marketing quality control of medicines and is one of the most important duties of national regulatory authorities. In collaboration with the Cameroonian National Drug Quality Control and Valuation Laboratory, the decision was made to initiate a prevalence study to assess the quality of antiinfective medicines in Cameroon. A total of 150 samples of ciprofloxacin tablets and 142 samples of metronidazole tablets were collected from 76 licensed pharmacies and 75 informal vendors in three cities in Cameroon using a random strategy wherever possible and a mystery shopper approach. Three tests were carried out on each of the samples. Visual inspection allowed to find two falsified samples (0.7%) due to lack of information about the manufacturing company, and five more samples (1.7%) were deemed to be substandard due to flaws in the product. An additional 13 samples (4.5%) failed disintegration testing, and six (2.1%) others failed high-performance liquid chromatography assay testing due to insufficient active pharmaceutical ingredient (API) content. All samples were found to contain some API. A prevalence of 7.9% substandard or falsified (SF) medicines was found. Moreover, the prevalence of outlets selling SF medicines was greater in the informal sector (26.7%) than in the formal sector (2.6%). Although the prevalence of SF medicines found was low, efforts need to be made by national regulatory authorities to monitor the pharmaceutical market more closely.

A Review on Modern Trends in Analytical Instruments

Pharmaceutical analysis stands as an essential cornerstone within the pharmaceutical sector, playing a critical role in upholding the safety, effectiveness and quality of medicinal products. This scientific discipline encompasses a range of techniques for scrutinizing pharmaceutical compounds, dosage formulations and associated materials, with its primary mission being the fulfilment of regulatory standards and the preservation of public well-being. In this review, we mainly focussed on the modern trends in analytical instruments that include miniaturization & portable devices, multimodal & hybrid instruments, high resolution imaging techniques, data driven approaches, spectroscopy advancements, mass spectrometry innovations, advancements in chromatography, emergence of electrochemical sensors and nanotechnology integration. In pharmaceutical analysis, the horizon of innovation and transformation is being explored with enthusiasm and determination. The visionaries of this evolving landscape are the dedicated pharmaceutical analysts, scientists and researchers. They are at the forefront of pioneering the advancements that promise to reshape drug development, quality control and healthcare.

Ultrasensitive determination of metronidazole using flower-like cobalt anchored on reduced graphene oxide nanocomposite electrochemical sensor

Till now, the reported electrochemical sensors for metronidazole detection generally limited to the micromole per liter level, the trace detection in the low concentration range (nanomole per liter level) cannot be realized, which cannot meet the need for metronidazole determination at low concentrations in real clinical samples. In this work, a simple one-pot hydrothermal reduction method was applied to synthesize flower-like cobalt anchored on reduced graphene oxide (f-Co@rGO) nanocomposite. The prepared f-Co@rGO/GCE electrochemical sensor realize ultrasensitive quantitative determination of metronidazole in nanomole per liter level, obtained a wide linear detection range of 0.025–500 nM and a low detection limit of 0.015 nM (S/N = 3), far better than previous works. Moreover, the prepared sensor was successfully used for accurate determination of metronidazole in real serum samples, got a satisfied result. The f-Co@rGO/GCE electrochemical sensor has wide application prospects in clinical monitoring and drug quality control of metronidazole.

Selective Chemical Labeling Strategy for Oligonucleotides Determination: A First Application to Full-Range Profiling of Transfer RNA Modifications.

To date, the extremely high polarity and poor signal intensity of macromolecular nucleic acids are greatly impeding the progress of mass spectrometry technology in the quality control of nucleic acid drugs and the characterization of DNA oxidation and RNA modifications. We recently described a general N-(tert-butyldimethylsilyl)-N-methyl-trifluoroacetamide (MTBSTFA) labeling method for oligonucleotide determination and applied it to the full-range profiling of tRNA in vitro and in vivo studies for the first time. The primary advantages of this method include strong retention, no observable byproducts, predictable and easily interpreted MS2 data, and the circumvention of instrument harmful reagents that were necessary in previous methods. Selective labeling of N-(tert-butyldimethylsilyl)-N-methyl-trifluoroacetamide to the terminal phosphate groups of oligonucleotides endows it broadly applicable for DNA/RNA profiling. Moreover, the improvement of sequence coverage was achieved in yeast tRNAphe(GAA) analysis owing to this method's good detection capability of 1-12 nucleotides in length. We also extended this strategy to determine the abundance of modified bases and discover new modifications via digesting RNA into single-nucleotide products, promoting the comprehensive mapping of RNA. The easy availability of derivatization reagent and the simple, rapid one-step reaction render it easy to operate for researchers. When applied in characterizing tRNAs in HepG2 cells and rats with nonalcoholic fatty liver disease, a fragment of U[m1G][m2G], specific for tRNAAsn(QUU) in cells, was significantly upregulated, indicating a possible clue to nonalcoholic fatty liver disease pathogenesis.

Determinación de la actividad ansiolítica del extracto hidroalcohólico de las hojas de guayaba (Psidium guajava)

El objetivo fue determinar la actividad ansiolítica del extracto hidroalcohólico de las hojas de guayaba (Psidium guajava) en ratones (Mus musculus). La materia vegetal fue recolectada, secada, triturada y macerada con etanol al 70% durante tres días para su concentración. Se realizó el control de calidad de la droga seca y del extracto concentrado, para posteriormente ejecutar el tamizaje fitoquímico e identificar los metabolitos secundarios presentes en la planta. A continuación, el extracto se concentró hasta dejarlo seco y libre de alcohol. Para evaluar la actividad ansiolítica, se utilizaron 30 ratones machos con un peso de 25 - 30 g y una edad de 2 - 3 meses. Se utilizó propilenglicol al 15% como control negativo, Clonazepam como control positivo y los extractos a concentraciones de 25, 100, 200 y 300 mg/Kg. Se realizaron pruebas no condicionadas, con los equipos de: Cuarto Claro-Oscuro, Laberinto en Cruz Elevado y Campo Abierto. El comportamiento de los ratones en los distintos equipos fue grabado para posteriormente procesarlos en los programas ITOPI (Cuarto Claro-Oscuro y Laberinto en Cruz Elevado) y EMIS (Campo Abierto). Los datos fueron analizados en el programa IBM® SPSS® statistics versión 22, determinando que las dosis de 200 y 300 mg/Kg presentan mayor actividad ansiolítica sin afectar la locomoción de los biomodelos.

Anatomical and histochemical characterization of the vegetative organs of Talinum fruticosum (L.) Juss.

Talinum fruticosum (L.) Juss. is popularly known as beldroega and bredo, its leaves are highly nutritious consumed as a substitute for spinach, presenting considerable concentrations of pro-vitamin A, calcium and iron. In addition, its leaves are used in the management of cardiovascular diseases, having immunomodulatory properties. In view of this, the objective of the study was to carry out the anatomical and histochemical characterization of the vegetative organs of T. fruticosum. For this, the usual methods in plant anatomy were used to make semi-permanent slides containing cross-sections of the root, stem, petiole and leaf blade and paradermal sections of the leaf blade of the species for analysis in optical microscopy light and polarized light. Histochemical tests were also performed using specific reagents in order to locate the metabolites in the fresh leaf blade through cross-sections. The main characters useful in identifying the species were: root with periderm with 4-5 cell layers and tetrarch vascular cylinder; stem with presence of angular collenchyma and druses in the parenchyma; petiole with open collateral vascular bundle and absence of collenchyma; amphistomatic leaf blade with paracytic stomata, midrib showing biconvex contour, uniseriate epidermis, annular collenchyma, mesophyll with 2-3 layers of palisade parenchyma and 5-6 layers of spongy parenchyma and presence of druses. In addition, through the histochemical study, the presence of lignin, druses of calcium oxalate and lipophilic compounds in the leaf blade was observed. The results presented are fundamental for the quality control of the plant drug and pharmacobotanical standardization of the studied species.

Pharmacobotanical study and phytochemical prospection of Mirabilis jalapa L.

Mirabilis jalapa L., popularly known as “Maravilha”, belonging to the family Nyctaginaceae Juss., is used in folk medicine to treat leukorrhea, itching, swelling, among other diseases. The study aimed to describe anatomical characteristics of root, stem and leaf; identify the sites of accumulation of metabolites in the leaves and perform phytochemical prospecting of the leaves of M. jalapa. In the study, the usual methods in plant anatomy were used in the preparation of the analyses of semi-permanent slides containing cross-sections of the root, stem, petiole and leaf blade and paradermal leaf blade of M. jalapa. Histochemical tests were also performed in order to locate the metabolites in the leaf blade through cross-sections and phytochemical prospection of methanolic extracts of the leaves, by means of Thin Layer Chromatography. For the root, layers of periderm and pheloderm were observed; on the stem the presence of phloem both near the xylem and the sclerenchyma; in the leaf blade, raffide-type crystals were observed only in the mesophyll region, and presenting amphistomatic leaf blade. For histochemistry it was observed that the crystals are calcium oxalate, in addition to observing phenolic compounds, alkaloids, steroids, lipophilic compounds and lignin. In the phytochemistry was identified mono and sesquiterpenes, triterpenes and steroids, flavonoids, cinnamic derivatives and reducing sugars. The results presented are fundamental for the quality control of the plant drug and the pharmacobotanical standardization of the studied species.

Evaluation of drug standards, quality control, and trade in medicinal plants

This article is about the importance of medicinal plants in the manufacture of Ayush formulations or exported as raw drugs. Granting a license to manufacture, conducting quality control tests, and enforcing the legal provisions of the Drugs & Cosmetics (D&C) Act 1940 are the responsibilities of the relevant statutory regulatory bodies. The main stakeholders responsible for ensuring the products' quality, safety, and effectiveness are licensed manufacturers who have to follow the standards prescribed under the statutory regulations. The widespread interest in Ayurvedic drugs and other plant-based products led to this appraisal of the achievements and challenges of the regulatory bodies and those responsible for accelerating the organised cultivation of medicinal plants for domestic use and for export.

Quantitative assessment of antioxidant potential of selected homeopathic preparations in clinical practice.

Antioxidant property like radical scavenging is a primary target to elucidate the efficacy mechanism of a drug against diseases linked to oxidative stress such as cancer, metabolic disorders, rheumatoid arthritis, etc. In alternative therapies, homeopathy is one of the preferred choices by patients and clinicians due to its potential to cure chronic and complex illnesses. However, the efficacy of homeopathic preparations at high diluted potencies attracts rational criticism due to insufficient scientific knowledge supporting the mechanism of action. Therefore, an attempt was made to estimate the total phenolic content (TPC) and radical scavenging activity of clinically prescribed homeopathic drugs. With gallic acid as a reference control, mother tinctures (MTs) and different potencies of Eucalyptus globulus (EG), Syzygium jambolanum (SJ), Ruta graveolens (RG), and Thuja occidentalis (TO) were used to perform Folin-Ciocalteu test, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. The results showed TPC of MTs equivalent to µg/mL of gallic acid viz; EG (4,872.5±133.2), SJ (8,840.5±14.8), RG (985.6±39.1), and TO (341.5±19.5) with significant ABTS and DPPH radical scavenging potential. Whereas 30C and 200C potencies of each homeopathic drug showed undetectable phenolic content and insignificant radical scavenging potential compared to vehicle control, i.e.,alcohol 90% (2.0±1.5). The reported efficacy of 30C and 200C potencies of homeopathic medicines against oxidative stress-related illnesses might be due to mechanisms other than radical scavenging. Furthermore, the assays studied can be helpful in drug standardization and quality control of MTs that are used as starting material in homeopathic preparations.

Onion-like Carbons Provide a Favorable Electrocatalytic Platform for the Sensitive Detection of Tramadol Drug.

This work reports the first study on the possible application of nanodiamond-derived onion-like carbons (OLCs), in comparison with conductive carbon black (CB), as an electrode platform for the electrocatalytic detection of tramadol (an important drug of abuse). The physicochemical properties of OLCs and CB were determined using X-ray diffraction (XRD), Raman, scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), and thermogravimetric analysis (TGA). The OLC exhibits, among others, higher surface area, more surface defects, and higher thermal stability than CB. From the electrochemical analysis (interrogated using cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy), it is shown that an OLC-modified glassy carbon electrode (GCE-OLC) allows faster electron transport and electrocatalysis toward tramadol compared to a GCE-CB. To establish the underlying science behind the high performance of the OLC, theoretical calculations (density functional theory (DFT) simulations) were conducted. DFT predicts that OLC allows for weaker surface binding of tramadol (E ad = -26.656 eV) and faster kinetic energy (K.E. = -155.815 Ha) than CB (E ad = -40.174 eV and -305.322 Ha). The GCE-OLC shows a linear calibration curve for tramadol over the range of ∼55 to 392 μM, with high sensitivity (0.0315 μA/μM) and low limit of detection (LoD) and quantification (LoQ) (3.8 and 12.7 μM, respectively). The OLC-modified screen-printed electrode (SPE-OLC) was successfully applied for the sensitive detection of tramadol in real pharmaceutical formulations and human serum. The OLC-based electrochemical sensor promises to be useful for the sensitive and accurate detection of tramadol in clinics, quality control, and routine quantification of tramadol drugs in pharmaceutical formulations.

The validated pharmaceutical standard operating procedure and quality control study of the coded polyherbal tablet formulation AYUSH SG-5

In India, Ayurvedic medicine has its own significance and dominance in the Indian Medicine System. The traditional medicine system of India is not well renowned due to the lack of standardization of herbal drugs. To assess the quality, purity, efficacy, potency, and safety of herbal drugs, standardization is the major aspect. Recently, World Health Organization (WHO) and European Medicines Agency (EMEA) have issued guidelines for the quality control of herbal drugs. The aim of the present study is the standardization of the coded polyherbal tablet formulation AYUSH SG-5. A scientific methodology was adopted to perform the standardization parameters like organoleptic parameters, microscopic, macroscopic, physico-chemical analysis, and high-performance thin-layer chromatographic (HPTLC) profiling of AYUSH SG-5. The HPTLC study has exhibited the presence of various phytochemicals such as 6-gingerol in Sunthi ( Zingiber officinale rhizomes), Epicatechin in Vetas (stem bark of Salix alba ), Colchicine in Suranjan ( Colchicum luteum corms), Resveratrol in Chopchini ( Smilax china tuber), Guggulsterone E & Z in Guggul ( Commiphora wightii resin). Based on the results of the present study, a monograph was proposed in the interests of quality control of the AYUSH SG-5. This research will help pharmacists to develop the formulation of AYUSH SG-5 with greater reproducibility and this document could be treated as a pharmaceutical standard operating procedure (SOP) for the production of AYUSH SG-5 in pharmacy. • A polyherbal ayurvedic tablet formulation AYUSH SG-5 for rheumatoid arthritis is prepared. • A scientific methodology was adopted to perform the standardization of AYUSH SG-5. • Organoleptic parameters, microscopic, macroscopic studies performed as per API. • Physico-chemical tests and HPTLC profiling of AYUSH SG-5 was performed. • In HPTLC study, marker compounds like 6-gingirol, Epicatechin, Colchicine, Resveratrol, guggulsterol E & Z in Guggul were identified. • A validated SOP was purposed for preparation and standardization of AYUSH SG-5.

Standardization of dry extracts from large cranberry leaves

Aim. To determine the parameters of standardization of a dry extract from large cranberry (Oxycoccus macrocarpus (Ait.)) leaves and a dry extract modified with arginine and develop projects of Drug Quality Control Methods (DQCM) for these substances.Materials and methods. The study object was dry extracts from large cranberry leaves. Leaves were harvested in October 2021 in the Zhytomyr region (Kostivtsi village, 50.326862437345945, 29.54310845594284). The extracts were obtained with a 50 % solution of ethyl alcohol in the ratio of 1:30 by double maceration. Half of the combined extract was dried to a dry extract (Extract 1), and the other half was modified with arginine in the threefold equimolar amount relative to the total amount of phenolic compounds and evaporated to a dry extract (Extract 2). Standard pharmacopoeial methods were used to determine standardization parameters. The quantitative determination was carried out using the spectrophotometric method by the content of flavonoids calculated with reference to hyperoside and hydroxycinnamic acids calculated with reference to chlorogenic acid on an Evolution 60S spectrophotometer (Thermo Scientific Spectronic, USA).Results and discussion. The parameters of standardization of dry extracts from large cranberry leaves were determined. The project of DQCM was proposed according to the following indicators: description, solubility, identification using the thin-layer chromatography method (by the content of flavonoids, hydroxycinnic acids and arginine), loss on drying, the residual amount of organic solvents (ethanol), microbiological purity, and the content of heavy metals. The assay was carried out using spectrophotometry by the content of flavonoids and derivatives of hydroxycinnic acids. Three batches of the extracts obtained, which fully corresponded to the projects of DQCM developed, were analyzed.Conclusions. The parameters of standardization of dry extracts from large cranberry leaves have been determined, and projects of DQCM for the substances obtained have been developed. It is the basis for creating new medicines for the correction of insulin-resistant conditions in Type 2 diabetes mellitus.

Fast and Ultrasensitive Glycoform Analysis by Supercritical Fluid Chromatography-Tandem Mass Spectrometry.

The glycoform of a therapeutic monoclonal antibody (mAb) has a significant impact on its effector function as well as its safety and pharmacokinetics. Glycoform heterogeneity is influenced by various factors, including the producing cells and cell culture processes. Therefore, accurate glycoform characterization is essential for drug design, process optimization, manufacturing, and quality control of therapeutic mAbs. In this study, we developed a fast, quantitative, and highly sensitive analytical platform for glycan profiling by supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) and applied the technique to the glycan structural analysis of mAbs. To achieve both the highest sensitivity and the most comprehensive glycan profiling, we integrated our energy-resolved oxonium ion monitoring (Erexim) method with SFC-MS to construct a new SFC-Erexim technology. An 8 min analysis of bevacizumab, nivolumab, ramucirumab, rituximab, and trastuzumab by SFC-Erexim detected a total of 102 glycoforms, with a detection limit of 5 attomoles. The dynamic range of glycan abundance was over 6 orders of magnitude for bevacizumab analysis by SFC-Erexim compared to 3 orders of magnitude for conventional fluorescence HPLC analysis. This method revealed the glycan profile characteristics and lot-to-lot heterogeneity of various therapeutic mAbs. We were also able to detect a series of structural variations in pharmacologically important glycan structures. The SFC-MS-based glycoform profiling method will provide an ideal platform for the in-depth analysis of precise glycan structure and abundance.

Cutting-edge mass spectrometry strategy based on imaged capillary isoelectric focusing (icIEF) technology for characterizing charge heterogeneity of monoclonal antibody

Imaging capillary isoelectric focusing (icIEF) technology has been becoming the gold criteria of monitoring monoclonal antibody (mAb) charge heterogeneity that is one of the major product-related variants in recombinant biopharmaceuticals, since the first commercial instrument developed twenty years ago. However, the protein identification in icIEF separation is just based on isoelectric point (pI) measurement of protein. Although high resolution mass spectrometry (HRMS) is currently the most powerful means of qualitative protein analysis, traditional icIEF cannot compatibly be used in conjunction with MS due to the use of less volatile reagents. In addition, protein heterogeneity characterization in depth such as peptide mapping by high performance liquid chromatography (HPLC) requires the focused protein bands to be collected as fractions after the icIEF separation, which is a great challenge in biopharmaceutical discovery. In this work, pembrolizumab was employed as targeting mAb (a highly selective anti-PD-1 humanized mAb), an integrated icIEF platform was developed including analytical profiling, MS coupling and fraction collections for charged variant preparation. Multiple operation modes can be rapidly and flexibly switched just by changing customized capillary separation cartridges without more configurations. Main component, four acidic variants (A1-A4) and three basic variants (B1–B3) were baseline separated then directly detected by icIEF-HRMS online coupling for rapid screening of intact protein heterogeneity where reliable and accurate molecular weight of protein charged variants were obtained. Next, by installing preparative capillary separation cartridge, fractions of major charge variants (A2-3 and B1-2) and main component were collected for following LC-MS peptide mapping characterization. The whole workflow of icIEF-based MS strategy for protein heterogeneity is straight forward, reliable and accurate, which provides a comprehensive and revolutionary technology for protein drug quality control (QC) monitoring, MS coupling for fingerprinting intact protein and HPLC-MS peptide mapping in depth.

Development of stability-indicating method for separation and characterization of benidipine forced degradation products using LC-MS/MS.

The present study describes forced degradation of benidipine (BEN) as per Q1A (R2) and Q1B guidelines of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. BEN degraded under hydrolysis (neutral, acidic, and alkaline), hydrogen peroxide induced oxidation, and UV light mediated photolytic degradation. A total of 14 degradation products (DPs) were found in all degradation studies, comprising 4 hydrolytic DPs, 8 oxidative DPs, and 4 photolytic DPs. A selective stability-indicating method was developed using an XBridge BEH C18 column with gradient elution program consisting of ammonium acetate (10mM, 4.8 pH, acetic acid) and acetonitrile. The flow rate was maintained at 1ml min-1 . All DPs were separated well using the developed HPLC method and were characterized using LC-MS/MS data. As this method is effective in identifying and separating BEN and its DPs with sufficient resolution, it can be used in laboratories for quality control of drugs in daily routine analysis and stability studies.

New Trends in the Quality Control of Enantiomeric Drugs: Quality by Design-Compliant Development of Chiral Capillary Electrophoresis Methods.

Capillary electrophoresis (CE) is a potent method for analyzing chiral substances and is commonly used in the enantioseparation and chiral purity control of pharmaceuticals from different matrices. The adoption of Quality by Design (QbD) concepts in analytical method development, optimization and validation is a widespread trend observed in various analytical approaches including chiral CE. The application of Analytical QbD (AQbD) leads to the development of analytical methods based on sound science combined with risk management, and to a well understood process clarifying the influence of method parameters on the analytical output. The Design of Experiments (DoE) method employing chemometric tools is an essential part of QbD-based method development, allowing for the simultaneous evaluation of experimental parameters as well as their interaction. In 2022 the International Council for Harmonization (ICH) released two draft guidelines (ICH Q14 and ICH Q2(R2)) that are intended to encourage more robust analytical procedures. The ICH Q14 guideline intends to harmonize the scientific approaches for analytical procedures’ development, while the Q2(R2) document covers the validation principles for the use of analytical procedures including the recent applications that require multivariate statistical analyses. The aim of this review is to provide an overview of the new prospects for chiral CE method development applied for the enantiomeric purity control of pharmaceuticals using AQbD principles. The review also provides an overview of recent research (2012–2022) on the applicability of CE methods in chiral drug impurity profiling.

Separation and identification of a complex flurbiprofen-polyethylene glycol mono- and diester mixture via a hyphenated HPLC-DAD-HRMS/SPE NMR system

We report the use of a hyphenated HPLC-DAD(diode array detector)-HRMS/SPE NMR system for the separation and isolation of a complex mixture of esters, containing substances with very similar LC retention times. The literature known mono- and diesters of the drug Flurbiprofen and polyethylene glycol, which form a large number of substances with varying chain lengths, were chosen for this study. We demonstrate the use of this hyphenated system to quickly and effectively isolate sixteen of these highly similar individual esters in an automated fashion, demonstrating its applicability in standard pharmaceutical analysis and quality control of drugs. Both, synthetic solutions of these esters and extracts from Flurbiprofen lozenges were used for this purpose. By the sole use of this system, the individual compounds were isolated and UV, HRMS and 1D and 2D NMR data could be collected, enabling the identification and differentiation of the individual esters.

ВЛИЯНИЕ КИСЛЫХ И ЩЕЛОЧНЫХ СРЕД НА ВРЕМЯ ПЛАВЛЕНИЯ ГИДРОФИЛЬНЫХ И ЛИПОФИЛЬНЫХ СУППОЗИТОРИЕВ

Abstract. In the pharmaceutical industry, disintegration testing is one of the most important methods for the development and quality control of drugs in the form of suppositories. Once inserted into a natural body cavity, the suppositories melt, soften, or dissolve in the rectal fluid and produce localized or systemic effects. The results of the active development of the excipients industry and the dynamics of the pharmaceutical ingredients market, the success of pharmaceutical technology, new principles of quality regulation dictate the need to analyze and generalize the current trends in the production of this dosage form. The purpose of this study is to show the effect of acidic (pH=4) and basic (pH=6) solvents on the melting time of both hydrophilic and lipophilic bases. Eleven formulas of different mixing concentrations of hydrophilic bases (polyethylene glycols) and one formula of a lipophilic base (Witepsol W37) were obtained by fusion. As a result of the experiment, it was found that the melting time of lipophilic bases (W37) was longer compared to hydrophilic bases in both acidic and basic environments. Among the hydrophilic suppositories, the formula containing PEG 4000 demonstrated a longer melting time compared to other formulas in both media. In addition, during the experiment, it was found that lipophilic bases (W37) are harder than hydrophilic ones in terms of characteristics, which may be due to including those with a higher melting point of fat-soluble than hydrosoluble suppositories. The results obtained led to the conclusion that suppositories based on hydrophilic bases (polyethylene glycol) have a shorter melting time in both acidic and basic solutions than lipophilic ones (Witepsol W37). Due to this, soluble drug compounds are more easily delivered to the site of action. That is, hydrophilic bases are more effective for the manufacture of vaginal suppositories.

Discovery and molecular elucidation of the anti-influenza material basis of Banlangen granules based on biological activities and ultra-high performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry

Ethnopharmacological relevanceTraditional Chinese medicine (TCM) has a wide range of applications, including human healthcare-associated treatments and bioactive compound discovery. However, complex chemical systems present a significant challenge for chemical-material-based research and quality control. For instance, Banlangen (BLG) granules is a well-acknowledged TCM preparation widely used in clinical treatment of virus infection. However, its chemical basis of anti-influenza efficacy remains unclear.Aim of the study: In the present study, a systematic discovery strategy for identifying anti-influenza molecules based on biological activities and chemical analysis was established to contribute to the molecular elucidation of the anti-influenza material basis of Banlangen granules. Materials and methodsHemagglutinase inhibition (HAI) and neuraminidase inhibition (NAI) assays were used to compare the anti-influenza activities of different fractions of BLG granules against H1N1, H5N1 and H7N9 viruses. A comparative qualitative analysis of the chemical constituents in BLG granules and their fractions was performed using ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS), in which a multiple mass spectrometry database platform and three compound identification strategies were used. The association between anti-influenza activities and chemical constituent characteristics was analyzed using multiple stoichiometries and data comparison strategies. ResultsThe results showed that the chromatography fractions F3 and F4 of the BLG granules had the highest anti-influenza activity. A total of 88 compounds were identified in the BLG granules, including 31 alkaloids, 16 organic acids, 10 nucleosides, 8 phenylpropanoids, 6 sulfur-containing compounds, 5 amino acids, 4 aromatic compounds, 3 aldehydes and ketones, 2 flavonoids, 1 alcohol, 1 carbohydrate, and 1 aliphatic compound. Out of these, 31 characteristic compounds were identified in fractions F3–F4 as candidate compounds with anti-influenza activity. Additionally, 6-methoxyquinoline and 4-guanidinobutanal were identified in BLG granules and its raw material (Isatidis Radix) for the first time. ConclusionIn this study, we proposed a systematic discovery strategy to thoroughly investigate the anti-influenza activity, chemical identification, and constituents-activity relationship of BLG granules. These data not only provided a deeper understanding of the molecular mechanism of the activity of BLG granules, but also presented a basis for the discovery of potential novel drug candidates and quality evaluation and control of BLG granules.