Application of diffusion-edited and solvent suppression 1H NMR to the direct analysis of markers in valerian-hop liquid herbal products

This is the peer reviewed version of the following article: Jose M. Prieto, Maria Mellinas-Gomez, Mire Zloh, ‘Application of diffusion-edited and solvent suppression 1H-NMR to the direct analysis of markers in valerian-hop liquid herbal products’, Phytochemical Analysis, Vol 27(2): 100-106, first published online January 13, 2016, which has been published in final form at doi: 10.1002/pca.2603 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving Copyright © 2016 John Wiley & Sons, Ltd.The rising trend to consume herbal products for the treatment and/or prevention of minor ailments together with their chemical and pharmacological complexity means there is an urgent need to develop new approaches to their quality and stability. This work looks at the application of one-dimensional diffusion-edited ¹H NMR spectroscopy (1D DOSY) and ¹H NMR with suppression of the ethanol and water signals to the characterization of quality and stability markers in multicomponent herbal medicines/food supplements. The experiments were performed with commercial tinctures of Valeriana officinalis L. (valerian), expired and non-expired, as well as its combination with Hummulus lupulus L. (hops), which is one of the most popular blends of relaxant herbs. These techniques did not require purification or evaporation of components for the qualitative analysis of the mixture, but only the addition of D2O and TSP. The best diagnostic signals were found at 7 ppm (H-11, valerenic acid), 4.2 ppm (H-1, hydroxyvalerenic acid) and 1.5-1.8 ppm (methyl groups in prenylated moieties, α-acids/prenylated flavones). This work concludes on the potential value of 1D DOSY ¹H NMR to provide additional assurance of quality in complex natural mixtures.Peer reviewe

Medicines informal market in Congo, Burundi and Angola: counterfeit and sub-standard antimalarials

BACKGROUND: The presence of counterfeits and sub-standards in African medicines market is a dramatic problem that causes many deaths each year. The increase of the phenomenon of pharmaceutical counterfeiting is due to the rise of the illegal market and to the impossibility to purchase branded high cost medicines. METHODS: In this paper the results of a quality control on antimalarial tablet samples purchased in the informal market in Congo, Burundi and Angola are reported. The quality control consisted in the assay of active substance by means of validated liquid chromatographic methods, uniformity of mass determination, disintegration and dissolution tests. Moreover, a general evaluation on label and packaging characteristics was performed. RESULTS: The results obtained on thirty antimalarial tablet samples containing chloroquine, quinine, mefloquine, sulphadoxine and pyrimethamine showed the presence of different kinds of problems: a general problem concerning the packaging (loose tablets, packaging without Producer name, Producer Country and sometimes without expiry date); low content of active substance (in one sample); different, non-declared, active substance (in one sample); sub-standard technological properties and very low dissolution profiles (in about 50% of samples). This last property could affect the bioavailability and bioequivalence in comparison with branded products and could be related to the use of different excipients in formulation or bad storage conditions. CONCLUSION: This paper evidences that the most common quality problem in the analysed samples appears to be the low dissolution profile. Here it is remarked that the presence of the right active substance in the right quantity is not a sufficient condition for a good quality drug. Dissolution test is not less important in a quality control and often evidences in vitro possible differences in therapeutic efficacy among drugs with the same active content. Dissolution profile can be dramatically affected by the choice of excipients in the oral solid formulation and, in many cases, is out of specifications due to the absence of formulation studies by producers of developing countries

Role of the list of standard terms in the European Pharmacopoeia for the establishment of the different existing pharmaceutical forms

The type and content of pharmacopoeias have changed many times over the years, until in 1964 the first European Pharmacopoeia was introduced under the jurisdiction of the Council of Europe as part of the implementation of the Convention on the Development of a European Pharmacopoeia.An important section of the European Pharmacopoeia is the list of standard terms. It is drawn up by the Commission of the European Pharmacopoeia, which is part of the European Directorate for the Quality of Medicines and Healthcare (EDQM), at the request of the European Commission, to be used in applications and marketing authorizations and packaging information, in the package leaflet, in the summary of product characteristics and in electronic communications.The main purpose of the study is to make a detailed analysis of the List of Standard Terms available in Bulgarian, as well as the database of standard terms maintained by the European Directorate for the Quality of Medicines in order to make a comparison between them and to identify the most the common dosage forms in them as well as the most common routes of administration.The results of the study show that the largest number are the standard terms referring to medicinal products intended for oral administration and injection. And the most common terms for dosage forms are those for solutions and powders. We also found that the most complete and up-to-date source of information on standard terms for medical devices is the database of standard terms maintained by the European Directorate for the Quality of Medicines, as it is constantly updated. Based on these facts, we can say that the European database is the gold standard for compiling lists of standard terms in each Member State of the Commission of the European Pharmacopoeia. The Bulgarian list of standard terms, on the other hand, is not updated often enough, it is recommended that this be done at shorter intervals, as new terms are constantly appearing. This is best done with each release of an updated version of the pharmacopoeia

Replacement, Reduction and Refinement of Animal Testing in the Quality Control of Human Vaccines

Vaccines are recognised as a highly cost effective tool for preventing infectious diseases. They are derived from biological sources and due to the complexity of composition and heterogeneity of products, vaccine lots undergo legally required quality control before they are released. Traditionally, laboratory animals have played an important role in quality control of vaccines and still, many laboratory animals are used in Europe for this purpose. Over the last decades, Replacement, Reduction and Refinement (3Rs) methods to classical animal tests have been developed by control authorities, academia and vaccine manufacturers. The purpose of this report is to inform the EURL ECVAM stakeholders on ongoing activities in development and validation of 3Rs methods for the quality control of vaccines for human use. The focus of the report is on methods for lot release testing (e.g. safety, pyrogenicity, potency) and projects related to the implementation of the consistency approach to established vaccines such as diphtheria, tetanus, pertussis and rabies vaccines.JRC.I.5-Systems Toxicolog

Evaluation of the Suitability of Kinetic Chromogenic LAL Assay for Determination of Endotoxin Levels in Heparin Sodium Injection

 Determination of the levels of endotoxins in injectable products has always been one of the concerns of regulatory authorities and manufacturers. Since a number of pharmaceuticals interfere with the LAL test to some degree, overcoming the inhibition or enhancement properties of a product is required as part of the validation of the LAL test for use in the final release testing of parenteral products. In this study, interference profile of Heparin injection in quantitative chromogenic LAL test was evaluated and the method of overcoming was investigated and validated. The results indicate that dilution as the most widely used technique for overcoming interference could not eliminate LAL interference in the aforementioned medicinal product. The inhibitory nature of heparin occurs due to its anticoagulant properties and can be overcome by using divalent cations such as magnesium. Three concentrations of magnesium chloride were evaluated for elimination of heparin’s inhibitory effect. All three concentrations studied (5, 10 and 25 mM) could effectively eliminate the inhibitory effects of heparin. Hence, one-way analysis of variance was used to determine statistically significant differences between these three concentrations. The results of ANOVA statistical method showed the optimal recovery of spiked endotoxin was at a concentration of 10 mM of magnesium chloride. In consequence, chromogenic LAL test using 10 mM of magnesium chloride as diluent could be a validated method of choice for heparin LAL assay.Highlights Bacterial endotoxins are important contaminants associated with injectable pharmaceuticals.Kinetic chromogenic LAL assay was used as the method to determine endotoxin levels in heparin injections.Selectivity, linearity and repeatability of the endotoxin chromogenic method was validated

Tablet splitting in elderly patients with dementia: The case of quetiapine

Quetiapine is an atypical antipsychotic approved for treating schizophrenia, bipolar depression, and mania but is frequently used in an off-label manner to control the behavioral and psychological symptoms of dementia in elderly patients with dementia. Due to the need to personalize doses for elderly patients with dementia, quetiapine tablet manipulation is widespread in hospital settings, long-term care facilities, and patient homes. The aim of this study was to assess the impact of the different splitting techniques on quetiapine fumarate tablets by analysing the obtained sub-divided tablets and to discuss compliance with the European Pharmacopoeia limits on whole and split tablets. Quetiapine fumarate tablets of two dose strengths were taken at random (in a number able to assure a power of 0.8 during statistical comparison) and were split with a kitchen knife or tablet cutter. The weight and the drug content were determined for each half tablet. The obtained data were compared to the European Pharmacopoeia limits. The differences between the different splitting techniques were statistically tested. Data showed that split tablets, independently of the dose strength and the technique employed, were not compliant with the European Pharmacopoeia specifications for both entire and subdivided tablets in terms of weight and content uniformity. Thus, such a common practice could have potential effects on treatment efficacy and toxicity, especially when also considering the fragility of the elderly target population in which polypharmacotherapy is very common. These results indicate a compelling need for flexible quetiapine formulations that can assure more accurate dose personalization

Provjera kakvoće cjepiva za sezonsku gripu

The purpose of seasonal influenza vaccination is to prevent its spread. The vaccines contain strains of the influenza virus recommended and approved for a particular season. Just like any other medicinal product, all vaccines require marketing approval. Batches of approved vaccines are extensively tested by the manufacturers and additionally controlled by the approving authorities, which issue the quality control certificates. This article not only to describes the legal background of quality control, but also how control test results obtained by a Croatian official control laboratory are compared to manufacturer’s results. We have found that testing results can slightly differ depending on methods/analytical procedures used in different laboratories. This investigation has also shown how important it is to test finished medicinal products, independently of testing at intermediate stages, and how retesting by control authorities ensures that marketed vaccines meet quality standards.Za prevenciju i suzbijanje širenja gripe kao zarazne bolesti svake se godine provodi sezonsko cijepljenje cjepivima koja u svom sastavu sadržavju sojeve virusa influence preporučene i odobrene za tu sezonu. Da bi se mogla staviti u promet, sva cjepiva moraju od nadležnog tijela dobiti dozvolu za stavljanje u promet kao i drugi lijekovi. Puštanje u promet proizvedenih serija odobrenog cjepiva zahtijeva osim opsežnih ispitivanja od strane proizvođača i dodatnu kontrolu od strane nadležnog tijela koje izdaje Certifi kat o provedenoj provjeri kakvoće temeljem kojeg se cjepivo kao imunološki lijek može staviti u promet. Cilj ovog rada je prikazati ne samo pravnu osnovu provjere kakvoće već i kako su uspoređeni rezultati dobiveni ispitivanjem u hrvatskome kontrolnom laboratoriju u odnosu na rezultate ispitivanja proizvođača. Rezultati pokazuju da postoje manja neslaganja rezultata ispitivanja različitih laboratorija koja su u ovisnosti s korištenim metodama/analitičkim postupcima (sličan ili identičan analitički postupak). Rezultati također pokazuju važnost ispitivanja koja se provode na gotovom proizvodu, neovisno o ispitivanjima provedenim na međuproizvodima, kao i važnost retestiranja koje provodi nadležno tijelo u svrhu osiguranja da se na tržištu nalaze samo imunološki lijekovi koji udovoljavaju zahtjevima kakvoće

Report concerning results of proficiency testing laboratory on assay of tobramycine and nystatin by microbiological method

The present study describes the results obtained by the Microbiological Control Laboratory from Institute for Control of Biological Products and Veterinary Medicines after participating in the proficiency testing scheme study on microbiological assay of nystatin and tobramycin. The proficiency testing scheme was organized by European Directorate for the Quality of Medicines and Health Care. The microbiological method consisted of a cylinderplate agar diffusion assay using Bacillus subtilis ATCC 6633 for tobramycin and Saccharomyces cerevisiae for nystatin as the test microorganism. The means of results were 108.70 % of label claim for nystatin and 104.70%of label claim for tobramicin. The Z scores were 0.14 for tobramycin and 1.40 for nystatin, the assigned value used for booth samples was 105.4% for tobramycin and 101.7% for nystatin. The performance of Microbiological Control Laboratory was very good for both samples

Pathological features and outcomes of incidental renal cell carcinoma in candidate solid organ donors

Background: We report the findings of a single Italian center in the evaluation of renal lesions in deceased donors from 2001 to 2017. In risk evaluation, we applied the current Italian guidelines, which include donors with small (< 4 cm, stage pT1a) renal carcinomas in the category of non-standard donors with a negligible risk of cancer transmission. Methods: From the revision of our registries, 2,406 donors were considered in the Emilia Romagna region of Italy; organs were accepted from 1,321 individuals for a total of 3,406 organs. Results: The evaluation of donor safety required frozen section analysis for 51 donors, in which a renal suspicious lesion was detected by ultrasound. Thirty-two primary renal tumors were finally diagnosed: 26 identified by frozen sections and 6 in discarded kidneys. The 32 tumors included 13 clear cell renal cell carcinomas (RCCs), 6 papillary RCCs, 6 angiomyolipomas, 5 oncocytomas, 1 chromophobe RCC, and 1 papillary adenoma. No cases of tumor transmission were recorded in follow-up of the recipients. Conclusion: Donors with small RCCs can be accepted to increase the donor pool. Collaboration in a multidisciplinary setting is fundamental to accurately evaluate donor candidate risk assessment and to improve standardized protocols for surgeons and pathologists

AN OVERVIEW ON PHARMACOPOEIAS IN THE WORLD AND MONOGRAPH ELABORATION TECHNIQUES

Pharmacopoeias are official sources that contain national and international rules that must be complied with legally and scientifically regarding substances, materials, drugs, devices and methods used in pharmaceutical field and pharmaceutical production. The monographs are consisted of general titles such as definition, production, characters, identification, tests, assay, storage, labelling and impurities. The World Health Organization states that sixtyeight different pharmacopoeia continue to be used effectively in fifty six countries around the world. In this review information about national and international wold pharmacopoeias, structure and general content of pharmacopoeias, and monograph elaboration techniques are given.                      Peer Review History: Received 26 April 2020; Revised 25 May; Accepted 3 July, Available online 15 July 2020 Academic Editor: Dr. Nuray Arı, Ankara University, Turkiye, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Dr. Mohammed Abdel-Wahab Sayed Abourehab, Umm Al-Qura University;  Makkah Al-Mukarramah, Saudi Arabia, [email protected] Heba M. Abd-El-Azim, Faculty of Pharmacy – Damanhour University, [email protected]