Galenic Preparations Research Articles

OILVEQ: an Italian external quality control scheme for cannabinoids analysis in galenic preparations of cannabis oil.

Italy legalized cannabis oil for specific medical conditions (neuropathic pain, refractory epilepsy and other established pathologies) in 2015, but mandates titration of principal cannabinoids before marketing each batch using iphenated techniques coupled with mass spectrometry. To assess reliability of laboratories from the Italian National Health Service in charge of titrating the batches, the Italian National Institute of Health set up an quality control program on determination of Δ9-tetrahydrocannabinol l (THC), cannabidiol (CBD), Δ9-tetrahydrocannabinolic acid A (THCA-A) and cannabidiolic acid (CBDA) in cannabis oil preparations. Two rounds of exercises have been carried out since 2019, involving sixteen Italian laboratories. Five different cannabis oil samples (19-1A and 19-1B for the first round and 22-1A, 22-1B and 22-1C for the second one were prepared and 1 mL amount of each sample was sent to the laboratories. The quantitative performance of each laboratory was assessed calculating the Z-score value, a statistical measurement for value's relationship to the mean of a group of values. In the first round, eight out of fourteen laboratories employed an LC-MS while the remaining six used GC-MS. Differently, in the second round, six out of eleven laboratories employed a GC-MS while the remaining five used LC-MS. In the first round, only 28.6 % laboratories achieved an acceptable performance (Z-score±2), and all of them used LC-MS as analytical method. In the second round, none of the laboratories achieved an acceptable performance. Satisfactory results, based on Z-scores, were generally low (0.0-75.0 %), with only one exception of 100 % for THCA-A determination in sample 22-1B. In the second round, three false negatives (two THC and one CBD by GC-MS determination) were reported while no false positives were described in the blank sample. The two rounds yielded a mean ERR% of 42 % approximately and a mean CV% around 70 % in GC-MS determination. When applying LC-MS determination, the two rounds yielded a mean ERR% of 36 % approximately and a mean CV% around 33 %. The obtained results underline the need for a clear and consistent protocol to be adopted by all laboratories intending to include the titration of oily cannabis-based products into their routinely analytical techniques. This emphasis on methodology standardization and participation to quality control schemes is essential for ensuring reliable and accurate measurements, ultimately enhancing the overall effectiveness and reliability of medical cannabis treatments.

Antidiarrheal effect of Psidium guajava L. extract in acute diarrhea: a systematic review.

Acute diarrheal diseases are a leading cause of childhood mortality and morbidity worldwide. Psidium guajava has been globally used for its antidiarrheal potential. We conducted a systematic review of scientific articles published up to the year 2021, which included in vivo pre-clinical tests and clinical trials involving patients with acute infectious diarrhea to verify the antidiarrheal, antibacterial and antispasmodic effects of galenic preparations or phytopharmaceuticals from P. guajava. PRISMA and Rayyan were used as tools for the selection of studies collected in four databases (Pubmed, Scopus, Web of Science and Science Direct). The keywords used to carry out the search were: 'Psidium guajava', 'guava', 'antidiarrhe*' and 'diarrhe*', joined by Boolean operators 'OR' or 'AND'. The characteristics of studies in animal models of acute diarrhea induction, as well as in vivo and in vitro motility and microbiological tests linked with its main pathophysiological mechanisms, were collected. Twenty-three articles were included. Twenty (87%) of these reported heterogenic preclinical studies, predominating pharmacological studies of efficacy against conventional antidiarrheal agents, which utilized relevant outcomes and models of infectious diarrhea from the top pathogens in the clinic along with classical castor oil-induced diarrhea associated with motility tests. Only three articles (13%) corresponded to clinical trials investigating the efficacy, dose and safety of these preparations. Most studies reported positive results and significant mechanistic evidence from antibacterial, anti-motility, anti-secretory and protective/anti-inflammatory perspectives. However, further studies are needed to define the clinical significance and safety treatment with P. guajava extracts. © 2024 Society of Chemical Industry.

Socialization of Community Knowledge Management about Pharmaceutical Products in Suka Damai Village, Langkat, North Sumatra

Socialization of public knowledge management about pharmaceutical products aims to provide information as a form of dissemination in the form of education. This community service was carried out in Suka Damai Village, Langkat district, North Sumatra Province. The purpose of this community service is to provide and practice knowledge about pharmaceutical products through traditional medicines which are mixed from plant ingredients, animal ingredients, mineral ingredients, galenic preparations, or mixtures of these materials. Traditional medicine can be made into a simple product that can be made and practiced by yourself, for example roll on aromatherapy or commonly called freshcare which has many uses in everyday life. Apart from that, other products such as dry instant ginger drinks can also be consumed with various benefits. The use of natural materials can also be used as a way to open business opportunities. Thus, people gain knowledge and know how to make one of the health products that so far when they want to use it they have to buy it first.

Myricetin as a Promising Flavonoid with Multitargeted Biological Activity

Polyphenolic compounds are widely represented in objects of plant origin and have diverse types of biological activity. Since ancient times, the beneficial effect of various galenic preparations on human health has been known, and they acted as almost the only source of treatment for various diseases and improvement of well-being. The major components of many herbal medicines are flavonoids, which are represented by both individual structures and related carbohydrate components. One of the widely represented flavonoids in plants is myricetin. This molecule belongs to one of the most hydroxylated compounds and has a wide range of therapeutic possibilities. This modern review summarizes the latest information on myricetin’s antioxidant, antidiabetic, anti-inflammatory, antiviral, neuroprotective, antitumor, hepatoprotective activity and its effect on the functioning of the cardiovascular system. From the latest results of studying the biological activity of myricetin, it is obvious that the polyphenolic compound is a promising substance for the prevention and complex therapy of various diseases. It should be noted that myricetin can be considered as a potential candidate for the targeted design of new substances with more pronounced pharmacological effects. In addition, the flavonoid finds application in various biologically active additives and food products, which expands the prospects of its research.

Phytochemical, Technological, and Pharmacological Study on the Galenic Dry Extracts Prepared from German Chamomile (Matricaria chamomilla L.) Flowers

Galenic preparations of German chamomile are used to treat mild skin diseases, inflammation, and spasms, and they have also been reported to have anxiolytic and sedative effects. The medicinal use of chamomile is well known in ethnomedicine. After obtaining its galenic preparations, there is lots of waste left, so it is expedient to develop waste-free technologies. The aims of this study were to gain knowledge of the ethnomedical status of chamomile in the past and present, develop methods for preparing essential oils and dry extracts from German chamomile flowers using complex processing, reveal the phytochemical composition of such extracts, and verify the analgesic and soporific activity of the extracts. Two methods for the complex processing of German chamomile flowers were developed, which allowed us to obtain the essential oil and dry extracts of the tincture and aqueous extracts as byproducts. A total of 22 phenolic compounds (7 hydroxycinnamic acids, 13 flavonoids, and 2 phenolic acids) were found in the dry extracts by using UPLC-MS/MS. In total, nine main terpenoids were identified in the chamomile oil, which is of the bisabolol chemotype. During the production of chamomile tincture, a raw material–extractant ratio of 1:14–1:16 and triple extraction are recommended for its highest yield. In in vivo studies with mice and rats, the extracts showed analgesic activity and improvements in sleep. The highest sedative and analgesic effects in rodents were found with the dry extract prepared by using a 70% aqueous ethanol solution for extraction at a dose of 50 mg/kg. The developed methods for the complex processing of German chamomile flowers are advisable for implementation into the pharmaceutical industry to reduce the volume of waste during the production of its essential oil and tincture, and to obtain new products.

Biomathematical approach determination of a rational formula of complex phytocompositions

Despite the huge achievements of pharmaceutical chemistry, herbal medicines based on medicinal plant raw materials (MPRMs) are still in demand for the treatment of both humans and animals diseases. Their main advantage is the small number of contraindications and side effects. In this case, not one but several phytocompositions are often used, which makes it possible to enhance the effectiveness of the drugs and expand the spectrum of action. The key point in creating multicomponent (galenic) preparations is the development of an accurate phytocomposition formula that best meets the set goals. This process is quite complex and timeconsuming. The purpose of this study was to determine the rational formula of complex phytocompositions based on a biomathematical approach. To reduce the number of performed experiments compared to blind enumeration and increase the reliability and efficiency of the quantitative formula of the phytocomposition, we tested a combination of the approach used in mathematics to search for the extremum of functions of many variables with a biological experiment on Parametium caudatum. In this case, the variables were the shares of each MPRM in the final recipe; function was understood as the pharmacological activity of a substance, determined through its membrane-stabilizing and antioxidant effect. This made it possible to determine the effective ratio of phytocomposition components faster and at lower costs. A comparison was made among more than 100 model samples. It has been established that all of them are non-toxic and have a good antioxidant and membranestabilizing effect. The final combination is by 10-20% more effective than other model samples and therefore it is advisable to use it in the future as the main ingredient for obtaining liposomal preparations for external use with a good pharmacological effect.

The Use of Shells of Marine Molluscs in Spanish Ethnomedicine: A Historical Approach and Present and Future Perspectives.

Since ancient times, the shells of marine molluscs have been used as a therapeutic and/or prophylactic resource. In Spain, they were part of practical guides for doctors or pharmacists until the 19th century. In general, seashells were prepared by dissolving in vinegar and were part of plasters or powders used as toothpaste, or to treat dyspepsia, heartburn and leprosy. Thus, the nacre or mother-of-pearl of various molluscs was regularly used in the Royal Colleges of Surgery and in hospitals during the times of the Cortes of Cadiz, as a medicine in galenic preparations based on powders. In contemporary Spanish ethnomedicine, seashells, with a high symbolic value, have been used as an amulet to prevent cracks in the breasts and promote their development during lactation, to avoid teething pain in young children, to eliminate stains on the face or to cure erysipelas. But, as in other countries, products derived from seashells have also been empirically applied. The two resources used traditionally have been the cuttlebone, the internal shell of cuttlefish and the nacre obtained from the external shells of some species. Cuttlebone, dried and pulverised, has been applied externally to cure corneal leukoma and in dental hygiene. In the case of nacre, a distinction must be made between chemical and physical remedies. Certain seashells, macerated in lemon juice, were used in coastal areas to remove spots on the face during postpartum. However, the most common practice in Spain mainland was to dissolve mother-of-pearl buttons in lemon juice (or vinegar). The substance thus obtained has been used to treat different dermatological conditions of the face (chloasma, acne), as well as to eliminate freckles. For the extraction of foreign bodies in the eyes, a very widespread traditional remedy has been to introduce small mother-of-pearl buttons under the lid. These popular remedies and practices are compared with those collected in classic works of medicine throughout history, and data on the pharmacological activity and pharmaceutical applications of the products used are provided. The use of cuttlebone powders is supported by different works on anti-inflammatory, immune-modulatory and/or wound healing properties. Nacre powder has been used in traditional medicines to treat palpitations, convulsions or epilepsy. As sedation and a tranquilisation agent, nacre is an interesting source for further drug development. Likewise, nacre is a biomaterial for orthopaedic and other tissue bioengineering applications. This article is a historical, cultural and anthropological view that can open new epistemological paths in marine-derived product research.

Analytical Method and Stability Study for Oral Suspension of Idebenone in Syrspend

Idebenone (IDB) (2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone) is a compound synthesized in the early 1980s. Initially developed for the treatment of cognitive disturbances and Alzheimer’s disease, IDB is now studied for Friedreich’s ataxia, Leber’s hereditary optic neuropathy (LHON), or Duchenne muscular dystrophy. The greatest disadvantage of IDB is its low solubility in water, resulting in low bioavailability. Galenic preparations of IDB in customized doses are common for pediatric patients, which can often prove to be the only option for access to therapy. As an antioxidant, the chemical stability of IDB is an essential guarantee for exerting the desired antioxidant action. Stability studies are essential to know the effect of storage conditions of a galenic product. For the first time, a stability-indicating LC-MS method has been developed to define the stability of IDB suspensions in SyrSpend® Sugar-Free Unflavored (Fagron), a carrier phase formulated for setting up suspensions of active pharmaceutical ingredients (APIs) insoluble or poorly insoluble in water and compatible with it. The proposed method was validated for linearity, accuracy, specificity, robustness, matrix effect and recovery, limit of detection (LOD), limit of quantification (LOQ), and repeatability.

Phytocannabinoid-rich galenic preparations for topical administration: extraction and stability testing.

Although medical cannabis was legalized in Czechia in 2013 and its use in topical treatments of skin disorders is now allowed, galenic formulations prepared from medical cannabis have not been widely implemented in the Czech healthcare system. One of the main reasons is the lack of a straightforward standardized protocol for their preparation. Cannabinoids, e.g., cannabidiol (CBD) and tetrahydrocannabinol (THC), have been shown to have therapeutic effects on various skin conditions, such as atopic dermatitis, psoriasis, scleroderma, acne and skin pigmentation. Recognizing the potential of dermatological treatment with medical cannabis, the present study aimed to evaluate the extraction capacity of various pharmaceutical bases for cannabinoids and the stability of prepared galenic formulations for dermatological applications with respect to cannabinoid content. The results showed that the stability of cannabinoids in formulations depended on the bases' physical and chemical properties. The highest THC decomposition was observed in cream bases and Vaseline, with estimated percentage loss of total content of up to 5.4% and 5.6% per week, respectively. In contrast, CBD was more stable than THC. Overall, the tested bases were comparably effective in extracting cannabinoids from plant material. However, olive oil and Synderman bases exhibited the highest cannabinoid extraction efficiencies (approximately 70%) and the best storage stabilities in terms of the content of monitored compounds. The proposed preparation protocol is fast and easily implementable in pharmacies and medical facilities.

Pid-Based Bottle Shark Heart Heater Design and Development

Traditional medicines are ingredients or ingredients in the form of plant ingredients, animal ingredients, mineral ingredients, galenic preparations, or mixtures of these materials, which have been used for generations for treatment and can be applied according to the norms in force in society. Bottle shark (Centrophorus atromarginatus) has good prospects as a producer of liver oil; this fish is easy to catch and occurs in relatively large quantities in Indonesian waters. The catch rate until now is only 39% of its sustainable potential. Bottled shark liver oil contains 90% squalene, Vitamin A, and Omega, which are very useful for the human body as a supplement for heart disease and stomach ulcers and increase stamina and brain intelligence. The rapid Development of technology certainly benefits the people who use it. One example of today's use of technology is applying a technology system for the fisheries sector. This tool works automatically to monitor the processing of bottled shark livers. That way, fishermen don't have to worry about cloudy weather or things that will take longer than processing the shark liver bottle. This Bottle Shark Liver Heater uses temperatures at 31˚, 32˚, 33˚, 34˚, and 35˚. With PID (Proportional Integral Derivative) control, the quality of the Bottle Shark liver can be maintained. This tool is supported by a DS18B20 temperature sensor, Arduino uno, Relay, Ceramic Heater element, DC Fan, LCD 16X12, Power Supply, and Switch. It is hoped that the community, with this automatic system device, can make it easier to manage Bottle Shark Liver Oil.

Socialization Of Community Knowledge Management About Pharmaceutical Products In Suka Damai Village, Langkat, North Sumatra

Socialization of public knowledge management about pharmaceutical products aims to provide information as a form of dissemination in the form of education. This community service was carried out in Suka Damai Village, Langkat district, North Sumatra Province. The purpose of this community service is to provide and practice knowledge about pharmaceutical products through traditional medicines which are mixed from plant ingredients, animal ingredients, mineral ingredients, galenic preparations, or mixtures of these materials. Traditional medicine can be made into a simple product that can be made and practiced by yourself, for example roll on aromatherapy or commonly called freshcare which has many uses in everyday life. Apart from that, other products such as dry instant ginger drinks can also be consumed with various benefits.The use of natural materials can also be used as a way to open business opportunities. Thus, people gain knowledge and know how to make one of the health products that so far when they want to use it they have to buy it first.

Pelatihan Pembuatan Jamu Instan Pada Masyarakat Di Desa Kemanisan Kecamatan Curug Serang Sebagai Upaya Peningkatan Kemandirian Ekonomi Keluarga

Traditional medicines are ingredients in the form of plant ingredients, animal ingredients, mineral ingredients, galenic preparations, or mixtures of these materials which have been used for generations for treatment and can be applied in accordance with the norms in force in society, while herbal medicine is a Traditional Medicine made in Indonesia. The purpose of this research is to increase understanding of the importance of increasing understanding regarding the processing of instant herbal medicine and raising awareness of the importance of improving skills in the form of training on making good and correct instant herbal medicine in Kemanisan village. The community service method used in this research is in the form of community relations through counseling and health training. The results showed that the knowledge level of the respondents before the training, namely 41,7 %, was in the sufficient category. The respondents' knowledge level after the training was 50% in the good category. Based on the study results, it can be concluded that the respondents' knowledge level before and after counseling and training increased their knowledge. Community service activities through counseling methods can increase respondents' knowledge regarding managing medicinal plants into an instant herbal products with economic value.

A description of Cannabinoid levels in Cannabis oil by high-performance liquid chromatography-mass spectrometry in a reference laboratory of North-Italy

BackgroundCannabis oils from FM2®, Bedica®, Bediol®, Bedrocan®, Bedrolite® and Pedanios 22/1® are largely used for medical purposes such as spasticity, chronic pain and appetite stimulating. Several studies showed cannabinoids action on CB1 and CB2 receptors reduces the hyperalgesic phase in inflammatory pain, leading to an improvement of conditions. The active compounds of these galenic preparations show a high variability making titration mandatory. For this reason, the exact oil composition knowledge is fundamental for personalizing therapy. This amis at adapting the correct dose to the patient, improving safety and efficacy of the galenic formulation, choosing the best preparation for each patient. PurposeThe aim of this study was to investigate oil preparations variability among different galenic laboratories in order to highlight the importance of titration activity. MethodsCannabis pharmacological active compounds titration has been performed in a large cohort of galenic laboratories in Italy. CBD, CBN, THC, THCA and CBDA quantification was carried out by a previous validated method in UHPLC-MS/MS. ResultsA number of 4318 samples of Cannabis oil from 83 pharmacies between January 2021 and February 2022 were evaluated. All galenic preparation specialities showed statistically significant differences among galenic laboratories (p-value < 0.001). THCA and CBDA concentrations were investigated as percentage of the extration yelds for total THC and CBD: these compounds had different values in the same specialities among distinct galenic laboratories. Moreover, seasonal variability in analytes concentrations was observed. ConclusionThis study described a wide range of oily samples from a large number of galenic laboratories, compared to published papers. In conclusion, knowledge of the exact oil composition is fundamental in the perspective of personalized therapy. Further studies aiming at the correlation between galenic composition and cannabinoids pharmacokinetics, clinical outcomes and toxic effects could be useful to improve our knowledge.

Possibilities of phytotherapy in the treatment of acute respiratory infections in children

Тhe article discusses the issue of the features of the course and treatment of ARI in children at the present stage. It is emphasized that the irrational use of antibiotic therapy leads to increasing antibiotic resistance, to the development of side effects. In order to improve the effectiveness of therapy, the use of traditional medicine, in particular phytotherapy, is proposed. Phytotherapy is a scientifically based treatment with medicinal plants or their parts used in native fresh or dried form, as well as in the form of galenic preparations. This treatment is especially advisable in sensitive patients, in patients with comorbid and polymorbid conditions, in the presence of resistance to the drugs shown to the patient, to prevent the development of side effects, at the stage of rehabilitation, as well as for the prevention of various diseases. In order to treat ARI and its complications, the use of the phytotherapeutic drug Umkalor in treatment protocols is justified.

Cannabis-Based Oral Emulsion for Medical Purposes to Meet the Needs of Patients: Formulation, Quality and Stability.

Current Italian legislation provides that medical Cannabis can be administered orally as an extract if it has been titrated to determine the concentration of active molecules. In this context, there is a need to provide known and adequate quantities of active ingredients in order to guarantee uniform therapies that lead to the optimization of risks/benefits. This is fundamental considering that the limited availability on the market of registered Cannabis-based products for medical use means that prescribed therapies are usually prepared as galenic preparations. Consequently, the preparation procedures must be consistent with the instrumentation usually present in the laboratories of community pharmacies. In this context, the purpose of this work was to standardize the preparation procedure for oil-in-water (O/W) emulsions to exploit advantages in terms of ease of administration and dosage adjustment, but also to ensure the palatable organoleptic characteristics of the finished product. For the formulations being studied, in addition to the quality according to the directives set out in the European Pharmacopoeia, the stability was evaluated to assure adequate validity for therapeutic uses.

Mini-Tablets: A Valid Strategy to Combine Efficacy and Safety in Pediatrics.

In the treatment of pediatric diseases, mass-produced dosage forms are often not suitable for children. Commercially available medicines are commonly manipulated and mixed with food by caregivers at home, or extemporaneous medications are routinely compounded in the hospital pharmacies to treat hospitalized children. Despite considerable efforts by regulatory agencies, the pediatric population is still exposed to questionable and potentially harmful practices. When designing medicines for children, the ability to fine-tune the dosage while ensuring the safety of the ingredients is of paramount importance. For these purposes solid formulations may represent a valid alternative to liquid formulations for their simpler formula and more stability, and, to overcome the problem of swelling ability, mini-tablets could be a practicable option. This review deals with the different approaches that may be applied to develop mini-tablets intended for pediatrics with a focus on the safety of excipients. Alongside the conventional method of compression, 3D printing appeared particularly appealing, as it allows to reduce the number of ingredients and to avoid both the mixing of powders and intermediate steps such as granulation. Therefore, this technique could be well adaptable to the daily galenic preparations of a hospital pharmacy, thus leading to a reduction of the common practice of off-label preparations.

Supervision and Registration of Traditional Medicine Brand in Indonesia

Traditional medicine (herbal medicine, standardized herbal medicine, phytopharmaca (clinical-based herbal medicine), imported traditional medicine) is an ingredient or herb ingredients in the form of plant ingredients, animal ingredients, mineral ingredients, galenic preparations, or a mixture of such ingredients that have been used for treatment for generations, and can be applied by the norms prevailing in the society. This study aims to find out and analyze related to the supervision and registration of traditional medicine brands in Indonesia. This research uses a qualitative method with a normative juridical approach. Data collection techniques are carried out through library studies. It can be concluded that the supervision of traditional medicine brands' registration must be carried out to the maximum by the National Agency of Drug and Food Control (NADFC). This avoids the problems that will arise in the event of the obscurity of the surveillance process. Good and proper supervision must be based on the rule of law because Indonesia recognizes the Law's existe.

Innovative Clinical-Organizational Model to Ensure Appropriateness and Quality in the Management of Medical Cannabis: An Italian Regional Case.

This work focuses on the clinical-organizational model implemented in an Italian region (Liguria) to streamline the access procedures to galenic cannabis preparations. The competent local health care authority that takes care of tracing a virtuous path to obtain common, uniform and shared protocols and ensure high standards of care is A.Li.Sa. (Azienda Ligure Sanitaria), a public organization with the function of coordination, direction and governance of the health care in the regional hospitals and health facilities. To this purpose, different working groups and a board meeting have been set up with the main role to define and develop technical standards to be applied to the prescription, preparation and dispensing of pharmaceutical forms based on therapeutic cannabis. In particular, the galenic preparations provided by the Italian Ministry of Health, described in detail in the regional standard operating protocols, are described and discussed. Moreover, the most significant data monitored from 2018 to 2020 and collected by hospitals and the evaluation of those derived from local pharmacies and health facilities are presented, discussed and compared in regards to their adherence and coherence with the Italian Institute of Health (ISS) data.

Research in phytochemical composition and hypoglycemic activity screening of the dry extracts from bearberry leaves

Diabetes mellitus is a global medical and social issue. In the developed countries of the world, from 5 to 12% of the population are diagnosed with diabetes mellitus and, according to WHO prognosis, the level of this disease may increase to 30-35%. Type 2 diabetes is a disease that progresses over time, but the rational and systematic use of hypoglycemic synthetic drugs and phytopreparations can significantly delay the onset of insulin therapy. A promising source of BAS with a hypoglycemic effect is the raw material of plants of the Heather family, namely, bearberry leaves. However, on the Ukrainian market there are no domestic galenic and novo-galenic preparations based on biologically active substances of this raw material, which indicates the prospects for the development of new drugs, including those with hypoglycemic action. The aim. The aim of the study was to study the phytochemical composition and to carry out a screening of the hypoglycemic activity of dry extracts from bearberry leaves modified with various amino acids to identify promising substances with hypoglycemic action. Materials and methods. The objects of the study were 11 dry extracts from bearberry leaves, 10 of which were modified with various amino acids. The study of the phenolic compounds of the extracts was carried out by TLC, HPLC, and spectrophotometry. To assess the hypoglycemic activity of the extracts, two experiments were carried out - primary screening and oral glucose tolerance test. Results. Using TLC and HPLC, in the extracts obtained arbutin, gallic acid, 5 flavonoids were identified, among which hyperoside was dominant, 4 hydroxycinnamic acids, among which chlorogenic and caffeic acids were dominant, and their content was established. In the extracts obtained, main groups of phenolic compounds were quantified using a spectrophotometric method. Dry extracts from bearberry leaves, modified with cysteine, arginine and glutamic acid, showed the strongest hypoglycemic activity. Conclusions. The chemical composition of phenolic compounds and the hypoglycemic activity of dry extracts from bearberry leaves modified with 10 different amino acids were determined. The most promising substances turned out to be extracts modified with cysteine, arginine and glutamic acid; therefore, they are promising agents for the development of new drugs.

UHPLC-MS/MS Analysis of Cannabidiol and Its Metabolites in Serum of Patients with Resistant Epilepsy Treated with CBD Formulations.

Cannabidiol (CBD) is a promising therapeutic agent with analgesic, myorelaxant, and anti-epileptic actions. Recently, a purified form of CBD (Epidiolex®) has been approved by the European Medicines Agency (EMA) for the treatment of two highly-refractory childhood-onset epilepsies (Dravet and Lennox-Gastaut syndrome). Given the interindividual response and the relationship between the dose administered and CBD blood levels, therapeutic drug monitoring (TDM) is a valuable support in the clinical management of patients. We herein report for the first time a newly developed and validated method using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS) to evaluate CBD and its metabolites (i.e., cannabidiol-7-oic acid (7-COOH-CBD), 7-hydroxycannabidiol (7-OH-CBD), 6-α-hydroxycannabidiol (6-α–OH–CBD) and 6-β-hydroxycannabidiol (6-β–OH–CBD)) in serum samples. The method reached the sensitivity needed to detect minimal amounts of analytes under investigation with limits of quantification ranging from 0.5 to 20 ng/mL. The validation results indicated in this method were accurate (average inter/intra-day error, <15%), precise (inter/intra-day imprecision, <15%), and fast (8 min run time). The method resulted to be linear in the range of 1–10,000 ng/mL for CBD-COOH, 1–500 ng/mL for 7-OH-CBD and CBD and 1–25 ng/mL for 6-α–OH–CBD and 6-β–OH–CBD. Serum levels of CBD (88.20–396.31 and 13.19–170.63 ng/mL) as well as of 7-OH-CBD (27.11–313.63 and 14.01–77.52 ng/mL) and 7-COOH-CBD (380.32–10,112.23 and 300.57–2851.82 ng/mL) were significantly higher (p < 0.05) in patients treated with GW pharma CBD compared to those of patients treated with galenic preparations. 6-α–OH–CBD and 6-β–OH–CBD were detected in the first group and were undetectable in the second group. 7-COOH-CBD was confirmed as the most abundant metabolite in serum (5–10 fold higher than CBD) followed by 7-OH-CBD. A significant correlation (p < 0.05) between the dose administrated and a higher bioavailability was confirmed in patients treated with a GW pharma CBD preparation.