Quality Control Of Herbal Medicines Research Articles

Current status and future perspective of external herbal dispensaries preparing traditional herbal medicine in South Korea: the first National-Wide Survey results

BackgroundAn external herbal dispensary (EHD) is a type of pharmacy that provides various types of personalized herbal medicines (PHMs) to other traditional Korean medicine (TKM) institutions. Such dispensaries were legalized by the Ministry of Health and Welfare (MoHW) in 2008 in South Korea. The purpose of this study is to understand the current status of the EHD facilities and their quality controls and compare them with the good manufacture practice (GMP) guidelines to contribute to the establishment of the safety and quality control criteria for PHMs.MethodsWe contacted 107 EHD representatives or people in charge of the preparation of PHMs (TKM pharmacists) and invited them to complete a survey questionnaire; of the total, 81 responded. The survey questionnaire was developed in 3 stages: drafting, revision by external experts, and final editing. It consisted of 20 questions covering 3 sections: basic characteristics of EHDs, facility, and quality control. The survey was hosted online from December 2017 to January 2018 as guided by the MoHW.ResultsThe completion rate was 75.7% (n = 81). In terms of facilities, the five facilities (water supply, manufacture, pest control, hygiene management and warehousing) that corresponded to the legal requirements of EHD were mostly equipped, but the types of facilities and equipment differed. Two facilities (sterilization and cross-contamination that were not legally required for EHD were found to have mostly pharmacopuncture-EHD (P-EHD), but hardly any herbal medicine-EHD (H-EHD). In our findings regarding quality control of non-medicinal herbs, sensory evaluation that included checks for foreign bodies and deterioration were conducted. In terms of the quality control of herbal medicines, residual pesticides and heavy metals tests were performed and for pharmacopuncture, pH, salinity, sterility, and endotoxin tests along with gross examination were performed. In the end, we found that 6 of the 38 standard items as required by the Korea GMP were suitable.ConclusionsIn this study, detailed information for each existing EHD law was determined through a nationwide questionnaire. Moreover, the basis for its reflection in additional legal standards should be introduced so that safe herbal medicine can be prepared in EHDs.

Flavanols and triterpenoids from Myrianthus arboreus ameliorate hyperglycaemia in streptozotocin-induced diabetic rats possibly via glucose uptake enhancement and α-amylase inhibition

Myrianthus arboreus is use traditionally as an antidiabetic agent in Ghana. We reported the in vivo antidiabetic activity of its 70 % ethanol stem bark extract (MAB) which we found to be strongly concentrated in its EtOAc fraction using glucose uptake and enzyme inhibitory assays. The present study sought to investigate the in vivo hypoglycaemic and anti-hyperlipidaemic activity of this ethyl acetate fraction of MAB (MAB-EtOAc, 50 and 100 mg/kg) in streptozotocin (STZ)-induced diabetic rats for 21 days, isolate and evaluate the bioactive constituents responsible for the antidiabetic activity. In silico pharmacokinetic and toxicity properties of the most active compound was also determined. MAB-EtOAc significantly (p < 0.001) reduced the blood glucose levels while normalizing considerably the altered serum lipid parameters of the diabetic rats which was comparable to glibenclamide (5 mg/kg). Chemical investigation of MAB-EtOAc led to the isolation of seven known compounds including three flavanols which are reported for the first time in the plant: epicatechin (1), epigallocatechin (2), dulcisflavan (3), euscaphic acid (4), tormentic acid (5), sitosterol-3-O-β-d-glucopyranoside (6) and arjunolic acid (7). The compounds markedly inhibited the action of α-amylase and, except for 4 and 6, which stimulated considerably glucose uptake in C2C12 cells. Compounds 2, 3, 5, 6 and 7 which were further evaluated in STZ-induced diabetic rats demonstrated hypoglycaemic and anti-hyperlipidaemic activities which, however, were not comparable with MAB-EtOAc. Compound 3, the most active compound was predicted to be non-toxic, non-mutagenic, has reasonable oral bioavailability and a decent substrate for further drug development. The findings of this study show that the isolated compounds may contribute to the antidiabetic activity of M. arboreus and could serve as marker compounds for the quality control of herbal medicines that would be made from the plant.

Chromatographic Fingerprinting and Quantitative Analysis of Marker in the Extract of Gloriosa superba Tubers Collected from Some Region of Chhattisgarh

Background: Gloriosa superba (Family: Liliaceae) is commonly known as Kalihari in India and has been used by several indigenous communities to treat a snake bite, skin diseases and joint pain. It has been also scientifically reported for many pharmacological activities such as hypoglycaemic, hepatoprotective, anticancer, anti-inflammatory. Present work is an effort to develop validated HPTLC method for the detection and quantification of chief constituent in the tuber extract of Gloriosa superba. Methods: HPTLC analysis of tuber extract has been performed on Silica gel 60 F254 (10 cm×10 cm) plates with mobile phase consisting toluene, ethyl acetate and diethylamine (02:08:02, v/v/v). Densitometric scanning of the plate was performed at 371nm by using CAMAG TLC scanner III equipped with visionCATS version 2.4.17207.2 (CAMAG) and developed method was also validated for accuracy, precision and robustness as per ICH guidelines. Results: present work has confirmed the rich content of colchicine in tuber extract of Gloriosa superba. The calibration curve was linear in the selected range of 0.4-1.2 μg/spot and regression equation found to be y = 0.0285x + 0.0074. the correlation coefficient (r) was 0.9978 for the regression equation. The LOQ and LOD was 0.170 μg /spot and 0.056 μg /spot respectively. The average recovery of colchicine at three levels was 99.5, 98.6 and 99.6 %, which indicated the remarkable reproducibility of the method. Conclusion: findings revealed that the developed method is simple, precise, and accurate for quantitative analysis of Gloriosa superba; and it might be useful for quality control of herbal medicine.

Analysis of curcuminoids and volatile components in 160 batches of turmeric samples in China by high-performance liquid chromatography and gas chromatography mass spectrometry

Turmeric (Curcuma longa L.) is a popular herbal medicine worldwide. Curcuminoids and volatile constituents are its major bioactive components. To improve the quality control of turmeric, we determined the contents of three main curcuminoids in 160 batches of turmeric samples collected from five major production areas of China by HPLC, and analyzed the volatile components by GC/MS. The results indicated that samples with red cross sections (2.75 ± 0.82 mg/g) contained significantly higher amounts of curcuminoids than samples with yellow sections (1.23 ± 0.60 mg/g) (p < 0.001). This result was consistent with empirical standard of TCM pharmacists. The contents of curcuminoids in samples from Hainan (4.51±0.25%), Guizhou (3.17±0.41%), and Sichuan (2.25±0.54%) were relatively high and consistent. Moreover, the GC/MS profiles of turmeric may be affected by storage and processing. This study sets a good example for comprehensive quality control of herbal medicines.

The use of chemometrics in combination with molecular spectroscopic and chromatographic methods for authentication of Curcuma species: a review

Currently, the awareness and public concern in the authenticity of herbal medicines has increased significantly, therefore, analytical methods capable of detecting the adulteration practice must be available. The rhizomes of Curcuma species such as Curcuma longa and Curcuma xanthorriza are the target of adulteration due to its popularity as components in herbal medicine formulation. For the sake of quality control of herbal medicines, a rapid and reliable method must be developed for authentication studies. Molecular spectroscopy including UV-Vis, infrared (near and mid) and 1H-NMR spectroscopy, as well as chromatographic-based methods especially liquid chromatography, can be an ideal method for herbal authentication due to its simplicity, however, the spectra and chromatogram obtained are usually complex which are difficult to interpret. To overcome this obstacle, a statistical approach known as chemometrics was used to treat spectra data to be easily used for authentication purposes including discrimination and classification between authentic and adulterated herbal components. This review highlighted molecular spectroscopic method in combination with multivariate data analysis (chemometrics) for authentication of herbal components.

Development and Validation of an Hplc Quantitative Determination Procedure for Paeoniflorin in Dry Garden Peony Extract

Quality control of herbal medicines requires standardization of the contents of biologically active compounds. Therefore, development and validation of analytical procedures used for quality assessment of new medicines is relevant. Roots of garden peony (Paeonia lactiflora), which is a ancestor of European peony varieties, were standardized for paeoniflorin. The possibility of using HPLC for quantitative determination of paeoniflorin in dry garden peony extract was an important aspect of designing garden peony products. A chromatographic procedure was developed and validated for quantitative determination of paeoniflorin and inclusion in quality control regulations for dry garden peony extract.

Разработка и валидация методики количественного определения пеонифлорина в экстракте пиона садового сухом методом ВЭЖХ

Контроль качества лекарственных препаратов растительного происхождения предполагает нормирование содержания биологически активных веществ, поэтому актуальным направлением является разработка и валидационная оценка аналитических методик, используемых для оценки качества новых лекарственных препаратов. Стандартизация корней пиона молочноцветкового, который является предком европейских сортов пиона, осуществляется по содержанию пеонифлорина. Важным аспектом при создании препаратов на основе пиона садовых сортов является изучение возможности использования ВЭЖХ для количественного определения пеонифлорина в экстракте пиона садового сухом. Разработаны условия хроматографического определения и валидирована методика количественного определения пеонифлорина с целью включения в нормативную документацию по контролю качества экстракта пиона садового сухого.

Review on “Standardization an Imp Tool for Herbal Drug Development”

The medicinal plants are important source for pharmaceutical manufacturing. Medicinal plants &amp; herbal medicines account for a significant percentage of the pharmaceutical market. There is increasing awareness and general acceptability of the use of herbal drugs in today’s medical practice although most of these applications are not scientific. Herbal medicines are not a simple task since many factors influence the biological efficacy and Reproducible therapeutic effect. So it is necessary to improve safety of herbal drugs by developing certain quality control parameters &amp; by following the WHO guidelines for herbal medicines. This review seeks to enlighten the need to establish quality parameters for collection, handling, processing and production of herbal medicine as well as employ such parameters in ensuring the safety of the global herbal market. It is necessary to introduce measures on the regulation of herbal medicines to ensure quality, safety, efficacy of herbal medicines by using modern suitable standards &amp; GMP. The processes of good quality assurance and standardization of herbal medicines and products using various spectroscopic, chromatographic and electrophoretic methods were also discussed. In fact, the research field of quality control of herbal medicines is really an interdisciplinary research. It needs crossover of chemistry, pharmacology, medicine and even statistics to provide a platform for the quality control of traditional herbal medicines and further to discover the novel therapeutics composed of multiple chemical compounds.&#x0D; Keywords: Herbal drugs, Adulteration, Standardization, Chromatography, Electrophoresis, HP-LC and GC-MS.

Characterization and compatibility of dry extract from Annona muricata L. and pharmaceutical excipients

The aim of this study was to characterize and evaluate the compatibility of the dry extract (DE) of leaves of Annona muricata L. with pharmaceutical excipients usually used in the manufacturing of medicines. Characterization of the DE and binary mixtures of the extract and excipients was carried out using scanning electron microscopy (SEM), differential scanning calorimetry, thermogravimetry (TG) and Fourier transform infrared attenuated total reflection spectroscopy. Spray drying technique produced extract to form spherical and hollow particles revealed by SEM, with four stages of mass loss in the TG curve. Pre-formulation study showed compatibility between the extract and microcrystalline cellulose, lactose, croscarmellose sodium and sodium starch glycolate. New medicines containing herbal drugs enter the market every year, and our study demonstrates that thermoanalytical techniques can be used in the development and quality control of herbal medicines.

High-Throughput Immunological Analysis of Dictamni Cortex: Implication in the Quality Control of Herbal Medicine.

Quality inconsistency of herbal medicine is an obstacle that limits the extensive use and study of traditional Chinese medicine. Differences in environmental conditions and processing methods of herbal medicine often result in varying clinical outcomes in patients. Standard chemical markers used for the quality control (QC) of herbal medicine are usually the most abundant and characteristic components, which may not be therapeutically relevant or cannot comprehensively reflect the biological quality of the herbs. In view of this, a novel QC method for better assessment of herbal medicine has been developed via bioactivities analysis. Immunological activities of Dictamni Cortex, a typical herbal medicine for the treatment of various inflammatory diseases, from different geographical locations in China, were evaluated. Upon in vitro treatment of their water and ethanol extracts, distinct patterns of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-10, IL-6, IL-12p70, IL-1β, and chemokine CXCL8 were released from the lipopolysaccharides- and/or phytohaemagglutinin-stimulated human peripheral blood mononuclear cells (PBMC). Thus, in addition to the commonly used morphological, chemical, or DNA markers, the novel high-throughput profiling of inflammatory cytokines and chemokines of PBMC upon treatment with herbal extracts could be an important reference to help for the quality control of herbal medicine in the future.

Quality Markers of Traditional Chinese Medicine: Concept, Progress, and Perspective

Abstract As the most important complementary medication against a variety of diseases, traditional Chinese medicines (TCMs) have been extensively applied over thousands of years. Current quality control of herbal medicines, however, is in great dispute. Unlike chemical drugs, which have clear and validated quality standards, the content of only one (or a few) compounds of many herbs and preparations is currently assessed as an indicator of quality, even though the assessed compound(s) is neither closely associated with the efficacy nor representative of the medicine as a whole. Based on the clinical use, compatibility of multiple component prescriptions, and manufacturing process of TCM, the new concept of a TCM quality marker that was proposed in previous work is discussed further here. In addition, practical technological approaches are described for the qualitative analysis and quantification of TCMs including herbs, processed products, and preparations, which lead to the discovery and identification of specific chemicals as quality markers and new quality control patterns. The progress that has been made in TCM quality control is also addressed. This work provides useful information for the quality control of herbal medicines in the future.

Rapid profiling of alkaloid analogues in Sinomenii Caulis by an integrated characterization strategy and quantitative analysis

Alkaloids, the principal constituents in the caulis of Sinomenium acutum, have gained an increasing interest over the past decades since they are widely employed as a clinical treatment for rheumatoid arthritis. In the present study, an integrated characterization strategy by combining mass defect filtering-based structure classification (MDFSC) and diagnostic fragment-ion-based extension (DFIBE) was firstly proposed for rapid profiling of alkaloids in Sinomenii Caulis (SC) via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The rectangular MDFSC window could more accurately screen the target alkaloids of different types, and the DFIBE could facilitate the acquisition of characteristic fragment ions for structural elucidation of alkaloids. High-performance liquid chromatography (HPLC) fingerprints with principal component analysis (PCA) and hierarchical clustering analysis (HCA) was established for identifying the chemical markers and simultaneous determination of sinomenine, magnoflorine, menisperine, stepharanine and ehydrodiscretine. A total of 91 alkaloids, including 82 targeted ones (26 morphinans, 22 aporphines, 20 protoberberines and 14 benzylisoquinolines) were unambiguously identified or tentatively characterized in SC, and 14 of them were reported for the first time. Sinomenine and magnoflorine could be selected as chemical markers to evaluate the quality of SC from different localities. In conclusion, the proposed method provided a potential approach for chemical profiling and holistic quality control of herbal medicines.

Rapid simultaneous quantification of fructooligosaccharides in Morinda officianalis by ultra-high performance liquid chromatography.

Many Chinese herbal medicines with tonifying effects contain high levels of inulin fructooligosaccharides. These herbal medicines have high development and utilization value because of their effects against dementia, depression, and oxidative stress; on improving learning and memory ability; and on enhancing immunity. In this study, a method was developed for the separation and simultaneous quantitation of fructose, glucose, sucrose, and ten inulin fructooligosaccharides by ultra-high-performance liquid chromatography with evaporative light scattering detection within 10min. Separation was performed on an Amide column with gradient elution. The calibration curves for the 13 constituents showed good linearity (R2 >0.9991). The limits of detection and quantification were 10.78-33.44 and 35.94-124.81 μg/mL, respectively, and the recoveries ranged from 98.90 to 103.67%. This method was successfully used to quantify the 13 constituents in the Chinese herbal medicine Morinda officinalis. The contents of the ten inulin fructooligosaccharides ranged from 56.28 to 60.71%. This method is accurate, rapid and simple and can be used for quantitative analysis in the quality control of herbal medicines and functional foods.

Identification of anti-inflammatory components in Sinomenii Caulis based on spectrum-effect relationship and chemometric methods

The present study aimed to identify the anti-inflammatory components in Sinomenii Caulis (SC) based on spectrum-effect relationship and chemometric methods. A phytochemical investigation of SC extract was performed firstly and afforded eleven potential bioactive compounds. The HPLC fingerprints of 19 batches of SC samples were evaluated by the chemometric methods such as similarity analysis (SA) and hierarchical clustering analysis (HCA). The anti-inflammatory effects of these samples were determined by inhibition of Nitric Oxide (NO) production. Partial least squares regression (PLSR) and artificial neural network (ANN) were used to explore the spectrum-effect relationship of SC. The results indicated that there was a close correlation between chemical fingerprint and anti-inflammatory activity of SC, and peaks 8, 9, 12, 13, 14, 16, 19 and 22 might be potential anti-inflammatory compounds in SC. The verification experiments by testing individual compounds and a combination of them indicated that sinomenine (P8), magnoflorine (P13), menisperine (P16) and stepharanine (P19) were the major anti-inflammatory compounds in SC. Collectively, the present study established the spectrum-effect relationship mode of SC and discovered the anti-inflammatory compounds in SC, which could be used for exploration of bioactive components and quality control of herbal medicines.

An integration of UPLC-DAD/ESI-Q-TOF MS, GC–MS, and PCA analysis for quality evaluation and identification of cultivars of Chrysanthemi Flos (Juhua)

BackgroundChrysanthemi Flos (CF), as a popular traditional Chinese medicine (TCM), has five main cultivars in China, namely “Chuju”, “Boju”, “Gongju”, “Huaiju” and “Hangju”. Due to their habitats and processing methods, great quality variations occur yet no systematical study has ever been carried out to evaluate such variations. PurposeIn this study, we aim to establish a new approach that can serve both as a quality control method and as an identification method for cultivars of CF. MethodThe components in CF samples were identified by a combination of UPLC-ESI-Q-TOF/MS and GC/MS. Furthermore, a multimodal quantitative method was established by UPLC-UV coupled with principal component analysis (PCA) and the similarity evaluation system (SES), which was used to control and identify four cultivars of CF. Results18 compounds of flavonoids and caffeoylquinic acids were identified and ten of them were quantified using UPLC-ESI-Q-TOF/MS. Different cultivars of CF could be clearly distinguished with the fingerprints evaluation and principal component analysis (PCA). A total of 74 volatile compounds were detected by GC/MS. The distinctness of volatile components was observed. By the combination of UPLC-ESI-Q-TOF/MS and GC/MS, an identification and quality control method for CF was successfully established. ConclusionThe combination of UPLC-ESI-Q-TOF/MS and GC/MS could act as a comprehensive multimodal method for both identification and quality control of herbal medicines. This study provided new insights into the overall evaluation method for herbal medicines possessing different cultivars.

PROBLEMS OF COMPREHENSIVE CHEMICAL PROFILING OF MEDICINAL PLANTS

Interest and attention to phytotherapy in Russia are increasing every year, which is consistent with global trends. Ensuring the growing demand inevitably leads to the appearance of phytopreparations of low quality and efficiency, and sometimes to a complete falsification of plant raw materials and preparations from it. Therefore, the pharmaceutical safety and quality of plant raw materials, herbal preparations and medicines from plant raw materials are among the most important problems in the field of medicine, biomedicine, pharmacognosy and phytochemistry. The review considers modern methodological approaches to solving problems of the problems mentioned, various concepts of identification, evaluation of the authenticity and quality control of herbal medicines using markers of various types and instrumental methods of chromatographic profiling (one of the methods of metabolic research) of plant compositions, spectral and hyphenated methods used to solve these problems, the issues of standardization of plant raw materials, drugs in and medicines based on it, the world experience in solving problems of assessing the quality of plant raw materials and phytopreparations and the state of research in Russia.

Ethanol content in traditionally fermented ayurvedic formulations: Compromised Good Manufacturing Practice regulations – compromised health

ABSTRACT Background: A large part of the population of India prefers the traditional medicine (ayurvedic formulations) for primary health care. However, the effective quality control of herbal medicine is still a big challenge. Numerous reports indicate noncompliance with Compromised Good Manufacturing Practice (GMP) guidelines by the manufacturers which may lead to adverse drug reactions or toxic effects. Asava and arishta are the classical herbal dosage forms wherein fermentation occurs during production leading to the generation of ethanol. The presence of ethanol in these preparations may lead to their misuse. The self-generated ethanol is responsible for extraction of active constituents and acts as a self-preservative. As the procedure for preparation for asava and arishta is same, the ethanol content is also expected to be the same irrespective of the manufacturer. Objective: The objective of the present study was to assess and compare the ethanol content of some traditionally fermented ayurvedic formulations available in the market. Method: In this study, 20 formulations from 3 different manufacturers available as over-the-counter products were obtained and their ethanol contents were determined using gas chromatograph with flame ionization detector. Results: Statistically significant differences were noted in the ethanol content of various ayurvedic formulations. A simple, less time-consuming, economic, and validated gas chromatographic method for estimation of ethanol in fermented ayurvedic formulations was also developed successfully in present study. Conclusion: The data generated during study reflected poor compliance of GMP guidelines by the manufacturers and hence the quality is being grossly compromised posing a safety hazard.

The Prediction of Curcumin Content in the Turmeric Rhizome with Raman Handheld Spectroscopy

The quality control of herbal medicine should be started from the determination of the active substance at harvest time. The Raman spectrometry has been used for this propose. The aim of this study is to determine the quantification of curcumin in turmeric rhizome ( Curcuma longa Linn.) using Raman spectroscopy combined with multivariate analysis of PLS-R that are expected to provide reference method for quality control in turmeric rhizome, especially for raw materials of Herbal drugs. Parameters that can be used for analysis of curcumin levels on turmeric rhizome obtained using intensity of data Raman and the data obtained from the standard method will be processed with multivariate analysis methods PLS-R. The validation value of quantification result using Raman-PLSR is seen from R 2 value of 0.957, RMSEC value of 0,199 and p-value of 0.00. The study showed the developed method could be implemented on to determine the prediction quantification of raw material herbal medicine. Keyword : Curcumin, PLS-R, Turmeric, Raman Spectroscopy

CURRENT REQUIREMENTS FOR THE QUALITY OF HERBAL MEDICINAL PRODUCTS

The article provides the results of a comparative analysis of requirements laid out in the State Pharmacopoeia of the USSR, XI ed. (SPh XI) and the State Pharmacopoeia of the Russian Federation, XIII ed. (SPh XIII) concerning quality evaluation and standardization of herbal substances, herbal medicines and other herbal products. The article discusses requirements for the criteria of herbal substances and herbal medicines quality control described in general chapters and monographs that were previously in force and that have recently been adopted. The article mentions new herbal substances that were included into the State Pharmacopoeia of the Russian Federation for the first time as well as herbal substances included into the State Pharmacopoeia of the USSR, X ed., not included into SPh XI, but included into SPh XIII. The article analyses the requirements described in the new general chapters that were recently included into SPh XIII: “Herbal substances. Herbal preparations”, “Determination of heavy metals and arsenic content in herbal substances and herbal medicinal products”, “Determination of water absorption factor for herbal substances”, “Buds”, “Cut-pressed granules”. The article suggests ways to improve methods of analysis of herbal substances and herbal medicinal products in view of recent advances in pharmacopoeial analysis and the increasing requirements for its quality.

Identification of Confusable Herbal Medicines by Mapping of Partial Degradation Products from Herbal Medicine Polysaccharides.

Partial degradation products (PDPs) of herbal medicine (HM) polysaccharides with precolumn derivatization using 1-phenyl-3-methy-5-pyrazolone (PMP) were mapped by high performance liquid chromatography (HPLC), and three groups of confusable HMs were differentiated using the PDP fingerprints assisted with cluster analysis (CA). Three variables of HPLC mobile phase, i.e. acetonitrile proportion, buffer concentration and pH value were optimized with PDP of β-cyclodextrin. Radix Glehniae and Radix Adenophorae; Radix Sophorae Tokinensis and Rhizoma Menispermi; Radix Achyranthis Bidentatae and Radix Cyathulae were successfully distinguished by the method, respectively. The results involving mass spectrometry analysis showed that these PDPs primarily included oligosaccharides and a few monosaccharides. The method can be used as an effective approach for the identification and quality control of HMs, and can also facilitate the in-depth study of biological activity and further development of HM polysaccharides to some extent.