Search results for: drug administration

Authors: Magno Enrique Mendoza Meza

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This paper deals with the comparison of three control techniques: the hysteresis on-off control (HyOOC), the hybrid on-off control (HOOC) and the simple Structured Treatment Interruptions (sSTI). These techniques are applied to the mathematical model developed by Kirschner and Webb. To compare these techniques we use a cost functional that minimize the wild-type virus population and the mutant virus population, but the main objective is to minimize the systemic cost of treatment and maximize levels of healthy CD4+ T cells. HyOOC, HOOC, and sSTI are applied to the drug therapies using a reverse transcriptase and protease inhibitors; simulations show that these controls maintain the uninfected cells in a small, bounded neighborhood of a pre-specified level. The controller HyOOC and HOOC are designed by appropriate choice of virtual equilibrium points.

Keywords: virus dynamics, on-off control, hysteresis, multi-drug therapies

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Authors: Keaghan Brown

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The prioritization of drug resistance mutations impacting protein folding or protein-drug and protein-DNA interactions within macromolecular systems is critical to the success of treatment regimens. With a continual increase in computational tools to assess these impacts, the need for scalability and reproducibility became an essential component of computational analysis and experimental research. Here it introduce a bioinformatics pipeline that combines several structural analysis tools in a simplified workflow, by optimizing the present computational hardware and software to automatically ease the flow of data transformations. Utilizing preestablished software tools, it was possible to develop a pipeline with a set of pre-defined functions that will automate mutation introduction into the HIV-1 Integrase protein structure, calculate the gain and loss of polar interactions and calculate the change in energy of protein fold. Additionally, an automated molecular dynamics analysis was implemented which reduces the constant need for user input and output management. The resulting pipeline, Automated Mutation Introduction and Analysis (AMIA) is an open source set of scripts designed to introduce and analyse the effects of mutations on the static protein structure as well as the results of the multi-conformational states from molecular dynamic simulations. The workflow allows the user to visualize all outputs in a user friendly manner thereby successfully enabling the prioritization of variant systems for experimental validation.

Keywords: automated workflow, variant prioritization, drug resistance, HIV Integrase

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Authors: Bouzidi Abdelouahab, Ghadjati Nadhra, Bettihi Sara, Mahdeb Nadia, Daamouche Z. El Youm

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The effects of acute administration of TOTAL alkaloids, the main active principle of Datura stramonium, with toxic properties, were studied in female Albino-Wistar rats. After acute intraperitoneal administration of dose 120 mg kg-1 (≈1/3 DL50) of total alkaloids to the seeds of D. stramonium, there were no remarkable changes in general appearance and no deaths occurred in any experimental group. After 5 days a significant reduction was observed in total alkaloids of seeds. The Red Blood Cells (RBC), Hematocrit (HCT) and Hemoglobin (HGB) show significant changes in the treated groups. There were no statistical differences in Glutamic-pyruvic Transaminase (GPT), Alkaline Phosphatase (ALP), urea, glucose and total protein observed between groups. After 24 h Glutamic-Oxaloacetic Transaminase (GOT) and creatinine were significantly higher in the treated male rats than the control group histological examination of liver showed no histopathological changes.

Keywords: datura stramonium, rat, liver, kidney, alkaloids, toxicity

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Authors: S. Abd Rahim, F. A. Rahman, E. M. Nasir, N. A. Ramle

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Co-crystal is believed to improve the solubility and dissolution rates and thus, enhanced the bioavailability of poor water soluble drugs particularly during the oral route of administration. With the existing of poorly soluble drugs in pharmaceutical industry, the screening of co-crystal formation using carbamazepine (CBZ) as a model drug compound with dicarboxylic acids co-crystal formers (CCF) namely fumaric (FA) and succinic (SA) acids in ethanol has been studied. The co-crystal formations were studied by varying the mol ratio values of CCF to CBZ to access the effect of CCF concentration on the formation of the co-crystal. Solvent evaporation, slurry, and cooling crystallisations which representing the solution based method co-crystal screening were used. The product crystal from the screening was characterized using X-ray powder diffraction (XRPD). The XRPD pattern profile analysis has shown that the CBZ co-crystals with FA and SA were successfully formed for all ratios studied. The findings revealed that CBZ-FA co-crystal were formed in two different polymorphs. It was found that CBZ-FA form A and form B were formed from evaporation and slurry crystallisation methods respectively. On the other hand, in cooling crystallisation method, CBZ-FA form A was formed at lower mol ratio of CCF to CBZ and vice versa. This study disclosed that different methods and mol ratios during the co-crystal screening can affect the outcome of co-crystal produced such as polymorphic forms of co-crystal and thereof. Thus, it was suggested that careful attentions is needed during the screening since the co-crystal formation is currently one of the promising approach to be considered in research and development for pharmaceutical industry to improve the poorly soluble drugs.

Keywords: co-crystal, dicarboxylic acid, carbamazepine, industry

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Authors: Adriana Pereira Arteaga

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In many Latin American countries the transition towards legal pluralism - has developed as part of what is called Latin-American-Constitutionalism over the last thirty years. The aim of this paper is to discuss how legal pluralism in its current form in Bolivia may produce exclusion and violence. Legal sources and discourse analysis - as an approach to examine written language on discourse documentation- will be used to develop this paper. With the constitution of 2009, Bolivia was symbolically "re-founded" into a multi-nation state. This shift goes hand in hand with the "indigenista" and "decolonisation" ideologies developing since the early 20th century. Discourses based on these ideologies reflect the rejection of liberal and western premises on which the Bolivian republic was originally built after independence. According to the "indigenista" movements, the liberal nation-state generates institutions corresponding to a homogenous society. These liberal institutions not only ignore the Bolivian multi-nation reality, but also maintain the social structures originating form the colony times, based on prejudices against the indigenous. The described statements were elaborated through the image: the indigenous people humiliated by a cruel western system as highlighted by the constitution's preamble. This narrative had a considerable impact on the sensitivity of people and received great social support. Therefore the proposal for changing structures of the nation-state, is charged with an emancipatory message of restoring even the pre-Columbian order. An order at times romantically described as the perfect order. Legally this connotes a rejection of the positivistic national legal system based on individual rights and the promotion of constitutional recognition of indigenous justice administration. The pluralistic Constitution is supposed to promote tolerance and a peaceful coexistence among nations, so that the unity and integrity of the country could be maintained. In its current form, legal pluralism in Bolivia is justified on pre-existing rights contained for example in the International - Labour - Organization - Convention 169, but it is more developed on the described discursive constructions. Over time these discursive constructions created inconsistencies in terms of putting indigenous justice administration into practice: First, because legal pluralism has been more developed on level of political discourse, so a real interaction between the national and the indigenous jurisdiction cannot be observed. There are no clear coordination and cooperation mechanisms. Second, since the recently reformed constitution is based on deep sensitive experiences, little is said about the general legal principles on which a pluralistic administration of justice in Bolivia should be based. Third, basic rights, liberties, and constitutional guarantees are also affected by the antagonized image of the national justice administration. As a result, fundamental rights could be violated on a large scale because many indigenous justice administration practices run counter to these constitutional rules. These problems are not merely Bolivian but may also be encountered in other regional countries with similar backgrounds, like Ecuador.

Keywords: discourse, indigenous justice, legal pluralism, multi-nation

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Authors: Riccardo Bonazzi, Michaël Poli, Abeba Nigussie Turi

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This paper presents an applied research of a new module for the financial administration and management industry, Personalizable and Automated Checklists Integrator, Overseeing Legal Investigations (PACIOLI). It aims at designing the business model of the trust company of the future. By identifying the key stakeholders, we draw a general business process design of the industry. The business model focuses on disintermediating the traditional form of business through the new technological solutions of a software company based in Switzerland and hence creating a new interactive platform. The key stakeholders of this interactive platform are identified as IT experts, legal experts, and the New Edge Trust Company (NATC). The mechanism we design and propose has a great importance in improving the efficiency of the financial business administration and management industry, and it also helps to foster the provision of high value added services in the sector.

Keywords: new edge trust company, business model design, automated checklists, financial technology

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Authors: Arlinda Memetaj

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A sound system of administrative justice represents a vital element of democratic governance. The proper control of public administration consists not only of a sound civil service framework and legislative oversight, but empowerment of the public and courts to hold public officials accountable for their decision-making through the application of fair administrative procedural rules and the use of appropriate administrative appeals processes and judicial review. The establishment of effective public administration, has been since 1990s among the most 'important and urgent' final strategic objectives of the Republic of Macedonia. To this aim the country has so far adopted a huge series of legislative and strategic documents related to any aspects of the administrative justice system. The latter is designed to strengthen the legal position of citizens, businesses, civic organizations, and other societal subjects. 'Changes and reforms' in this field have been thus the most frequent terms being used in the country for the last more than 20 years. Several years ago the County established Administrative Courts, while permanently amending the Law on the General Administrative procedure (LGAP). The new LGAP was adopted in 2015 and it introduced considerable innovations concerned. The most recent inputs in this regard includes the National Public Administration Reform Strategy 2017 – 2022, one of the key expected result of which includes both providing effective protection of the citizens` rights. In doing the aforesaid however there is still a series of interrelated shortcomings in this regard, such as (just to mention few) the complex appeal procedure, delays in enforcing court rulings, etc. Against the above background, the paper firstly describes the Macedonian institutional and legislative framework in the above field, and then illustrates the shortcomings therein. It finally claims that the current status quo situation may be overcome only if there is a proper implementation of the administrative courts decisions and far stricter international monitoring process thereof. A new approach and strong political commitment from the highest political leadership is thus absolutely needed to ensure the principles of transparency, accountability and merit in public administration. The main method used in this paper is the descriptive, analytical and comparative one due to the very character of the paper itself.

Keywords: administrative justice, administrative procedure, administrative courts/disputes, European Human Rights Court, human rights, monitoring, reform, benefit.

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Authors: Samia Al-Shayban

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Conventionally, Fielding Author’s Farce is read as an attack on literary and theatrical establishment. This paper attempt to read it as a disguised scathing political attack upon, King George II, his court and administration. Fielding achieves his design through complex dramatization based on implicit connections between King George II and the poor poet Luckless who shifts his stand from defending the liberties of the authors into becoming one of their oppressors. Through the same connection, the king is accused of being the originator and protector of literary corruption. To strengthen the attack against the king, the court of nonsense which appeared in Luckless’ play is connected to George II’s court through the presence of opera and ignorance. Thus, Fielding’s literary dramatization is used as a medium to expose the corrupting influence of the ruling elite. The King, his court and administration are all complacent in devaluing the English theatre and turning it into a circus that generate nothing but ignorance and poverty. This practice is deliberately designed to keep people ignorant and authors poor so they remain unable to challenge their corrupt politics.

Keywords: fielding, King George II, ignorance, theatre, plays

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Authors: Wei-Ju Huang, Hung-Pin Hsu

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[Background] In congestive heart failure (CHF), it has always been the principle of clinical treatment to control the water retention mechanism in the body to prevent excessive fluid retention. Early control of sympathetic nerves, Renin-Angiotensin-Aldosterone system (RAA system, RAAS), or strengthening of Atrial Natriuretic Peptide (ANP) was the point. In RAA system, related hormones, such as angiotensin, or enzymes in the pathway, such as ACE-I, can be used with corresponding inhibitors to reduce water content.[Aim] In recent years, clinical studies have pointed out that if different mechanisms are combined, the control effect seems to be better. For example, recent studies showed that ENTRESTO, a combination of Sacubitril and Valsartan, is a good new drug for CHF. Sacubitril is a prodrug. After activation, it can inhibit neprilysin and act as a neprilysin inhibitor (ARNI) to reduce the breakdown of natriuretic peptides(ANP). Valsartan is a kind of angiotensin receptor blocker (ARB), both of which are used to treat heart failure at the same time, have excellent curative effects.[Materials and Methods] Considering the side effects of this drug, coughing and a few cases of diarrhea were observed. However, the effect of this drug on the patient's intestinal tract has not been confirmed. On the other hand, studies have pointed out that ANP supplement can improve the CHF and increase the inhibitory effect on cancer cells. Therefore, the purpose of this study is to use a special microbial detection method to prove that whether oral drugs have an effect on microorganisms.The experimental method uses Nissui Compact Dry to observe the situation in different types of microorganisms. After the drug is dissolved in water, it is implanted in a petri dish, and the presence of different microorganisms is detected through different antibody reactions to confirm whether the drug has some toxicology in the gut.[Results and Discussion]From the above experimental results, it can be known that among the effects of Sacubitril and Valsartan on the basic microbial flora of the human body, low doses had no significant effect on Escherichia coli or intestinal bacteria. If Sacubitril or Valsartan with a high concentration of 3mg/ml is used alone or under the stimulation of a high concentration of the two drugs, it has a significant inhibitory effect on Escherichia coli. However, in terms of the effect on intestinal bacteria, high concentration of Sacubitril has a more significant inhibitory effect on intestinal bacteria, while high concentration of Valsartan has a less significant inhibitory effect on intestinal bacteria. The inhibitory effect of the combination of the two drugs on intestinal bacteria is also less significant.[Conclusion]The results of this study can be used as a further reference for the possible side effects of the clinical use of Sacubitril and Valsartan on the intestinal tract of patients,

Keywords: sacubitril, valsartan, entresto, congestive heart failure (CHF)

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Authors: Aakanchha Jain, D. V. Kohli

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Cubosomes are nanoparticles but instead of the solid particles, cubosomes are self-assembled liquid crystalline particles of certain surfactant with proper ratio of water with a microstructure that provides unique properties of practical interest. Cubosomes encapsulating Fluconazole were prepared by emulsification method and characterized for particle size, entrapment efficiency. The cubosomes prepared were 257.2±2.94 nm in size with drug entrapment efficiency of 66.2±2.69%. The optimized formulation characterized for shape and surface morphology by TEM and SEM analysis. SEM photograph showed the smooth surface of optimized cubosomes and TEM photograph revealed square somewhat circular intact shapes of cubosomes. MIC was determined by XTT based method and antifungal activity was determined in vitro. The cumulative percentage of Fnz from cubosomes permeated via dialysis membrane (MWCO 12-14 KD) showed a percent cumulative drug release of 76.86% while Fnz solution showed release up to 91.04% in 24 hours in PBS (pH 6.5)(p < 0.005).

Keywords: Candids albicans, cubosomes, fluconazole, topical delivery

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Authors: Malab Sana Balouch, Meenakshi Nayar

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Hemispatial Neglect is a common disorder primarily associated with right hemispheric stroke, in the acute phase of which it can occur up to 82% of the time. Such individuals fail to acknowledge or respond to people and objects in their left field of vision due to deficits in attention and awareness. Persistent hemispatial neglect significantly impedes post-stroke recovery, leading to longer hospital stays post-stroke, increased functional dependency, longer-term disability in ADLs and increased risk of falls. Recently, evidence has emerged for the use of dopamine agonist Rotigotine in neglect. The aim of our Quality Improvement Project (QIP) is to evaluate and better the current protocols and practice in assessment, documentation and management of neglect and rotigotine use at the Neurorehabilitation unit at Charing Cross Hospital (CNRU). In addition, it brings light to rotigotine use in the management of hemispatial neglect and paves the way for future research in the field. Our QIP was based in the CNRU. All patients admitted to the CNRU suffering from a right-sided stroke from 2nd of February 2018 to the 2nd of February 2021 were included in the project. Each patient’s multidisciplinary team report and hospital notes were searched for information, including bio-data, fulfilment of the inclusion criteria (having hemispatial neglect) and data related to rotigotine use. This includes whether or not the drug was administered, any contraindications to drug in patients that did not receive it, and any therapeutic benefits(subjective or objective improvement in neglect) in those that did receive the rotigotine. Data was simultaneously entered into excel sheet and further statistical analysis was done on SPSS 20.0. Out of 80 patients suffering from right sided strokes, 72.5% were infarcts and 27.5% were hemorrhagic strokes, with vast majority of both types of strokes were in the middle cerebral artery territory (MCA). A total of 31 (38.8%) of our patients were noted to have hemispatial neglect, with the highest number of cases being associated with MCA strokes. Almost half of our patients with MCA strokes suffered from neglect. Neglect was more common in male patients. Out of the 31 patients suffering from visuospatial neglect, only 16% actually received rotigotine and 80% of them were noted to have an objective improvement in their neglect tests and 20% revealed subjective improvement. After thoroughly going through neglect-associated documentation, the following recommendations/plans were put in place for the future. We plan to liaise with the occupational therapy team at our rehab unit to set a battery of tests that would be done on all patients presenting with neglect and recommend clear documentation of outcomes of each neglect screen under it. Also to create two proformas; one for the therapy team to aid in systematic documentation of neglect screens done prior to and after rotigotine administration and a second proforma for the medical team with clear documentation of rotigotine use, its benefits and any contraindications if not administered.

Keywords: hemispatial Neglect, right hemispheric stroke, rotigotine, neglect, dopamine agonist

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Authors: Nopadol Burananuth, Tawatpupisit Pattaradapa

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The objective of this research is to study opinion of staff responsible for Quality Assurance. Research sample is 50 staff at Suan Sunandha Rajabhat University related to Quality Assurance works from each faculty and organization within the university. Data were analyzed using the computer program. The statistics used in data analysis were frequency, percentage, mean and standard deviation. The results reveal that most of the respondents were female, 92%, aged between 31-40 years, 44%. Most of them have been working on Quality Assurance for 1-3 years, 44%. The staff opinion survey showed that the operation received the highest score. In terms of Planning, committee appointment and job descriptions received the highest mean score. For Checking, acknowledging the results and reviewing quality in education received the highest mean score. For Acting, participating in the meeting in order to revise approach to Quality Assurance received the highest mean score. For Doing, planning an internal quality assurance by assigning period, budget and responsibilities received the highest mean score.

Keywords: education quality assurance, administration, staff, Suan Sunandha Rajabhat University

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Authors: Sunil K. Jena, Sanjaya K. Samal, Mahesh Chand, Abhay T. Sangamwar

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Tamoxifen (TMX) and its analogues are approved as a first line therapy for the treatment of estrogen receptor-positive tumors. However, clinical development of TMX has been hampered by its low bioavailability and severe hepatotoxicity. Herein, we attempt to design a new drug delivery vehicle that could enhance the pharmacokinetic performance of TMX. Initially, high-molecular weight carboxymethyl chitosan was hydrolyzed to low-molecular weight carboxymethyl chitosan (LMW CMC) with hydrogen peroxide under the catalysis of phosphotungstic acid. Amphiphilic block copolymers of LMW CMC were synthesized via amidation reaction between the carboxyl group of α-tocopherol succinate (TS) and an amine group of LMW CMC. These amphiphilic block copolymers were self-assembled to nanosize core-shell-structural micelles in the aqueous medium. The critical micelle concentration (CMC) decreased with the increasing substitution of TS on LMW CMC, which ranged from 1.58 × 10-6 to 7.94 × 10-8 g/mL. Maximum TMX loading up to 8.08 ± 0.98% was achieved with Cmc-TS4.5 (TMX/Cmc-TS4.5 with 1:8 weight ratio). Both blank and TMX-loaded polymeric micelles (TMX-PM) of Cmc-TS4.5 exhibits spherical shape with the particle size below 200 nm. TMX-PM has been found to be stable in the gastrointestinal conditions and released only 44.5% of the total drug content by the first 72 h in simulated gastric fluid (SGF), pH 1.2. However, the presence of pepsin does not significantly increased the TMX release in SGF, pH 1.2, released only about 46.2% by the first 72 h suggesting its inability to cleave the peptide bond. In contrast, the release of TMX from TMX-PM4.5 in SIF, pH 6.8 (without pancreatin) was slow and sustained, released only about 10.43% of the total drug content within the first 30 min and nearly about 12.41% by the first 72 h. The presence of pancreatin in SIF, pH 6.8 led to an improvement in drug release. About 28.09% of incorporated TMX was released in the presence of pancreatin in 72 h. A cytotoxicity study demonstrated that TMX-PM exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells. Pharmacokinetic studies on Sprague-Dawley rats revealed a remarkable increase in oral bioavailability (1.87-fold) with significant (p < 0.0001) enhancement in AUC0-72 h, t1/2 and MRT of TMX-PM4.5 than that of TMX-suspension. Thus, the results suggested that CMC-TS micelles are a promising carrier for TMX delivery.

Keywords: carboxymethyl chitosan, d-α-tocopherol succinate, pharmacokinetic, polymeric micelles, tamoxifen

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Authors: Mehrnaz Mostafavi

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Lung cancer is one of the most harmful forms of cancer. The long-term survival rate of lung cancer patients treated by conventional modalities such as surgical resection, radiation, and chemotherapy remains far from satisfactory. Systemic drug delivery is rarely successful because only a limited amount of the chemotherapeutic drug targets lung tumor sites, even when administered at a high dose. Targeted delivery of drug molecules to organs or special sites is one of the most challenging research areas in pharmaceutical sciences. By developing colloidal delivery systems such as liposomes, micelles and nanoparticles a new frontier was opened for improving drug delivery. Nanoparticles with their special characteristics such as small particle size, large surface area and the capability of changing their surface properties have numerous advantages compared with other delivery systems. Targeted nanoparticle delivery to the lungs is an emerging area of interest.Multimodal or combination therapy represents a promising new method to fight disease. Therefore, a combination of different therapeutic strategies may be the best alternative to improve treatment outcomes for lung cancer. Photothermal therapy was proposed as a novel approach to treatment. In this work, photothermal therapy with gold nanoparticles and near infrared laser (NIR) irradiation was investigated.Four types of small (<100nm), NIR absorbing gold nanoparticles (nanospheres, nanorods) were synthesized using wet chemical methods and characterized by transmission electron microscopy, dynamic light scattering and UV-vis spectroscopy. Their synthesis and properties were evaluated, to determine their feasibility as a photothermal agent for clinical applications. In vitro cellular uptake studies of the nanoparticles into lung cancer cell lines was measured using light scattering microscopy.Small gold nanorods had good photothermal properties and the greatest cellular uptake, and were used in photothermal studies. Under 4W laser irradiation, an increase in temperature of 10°C and decrease in cell viability of up to 80% were obtained.

Keywords: photothermal, therapy, cancer, gold nanorods

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Authors: Tsitsi Nyukurayi Muparari, Walter Timo De Vries, Jaap Zevenbergen

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The nature of Land administration accommodates diversity in terms of both spatial data handling activities and the expertise involved, which supposedly aims to satisfy the unpredictable demands of land data and the diverse demands of the customers arising from the land. However, it is known that strategic decisions of restructuring are in most cases repelled in favour of complex structures that strive to accommodate professional diversity and diverse roles in the field of Land administration. Yet despite of this widely accepted knowledge, there is scanty theoretical knowledge concerning the psychological methodologies that can extract the deeper perceptions from the diverse spatial expertise in order to explain the invisible control arm of the polarised reception of the ideas of change. This paper evaluates Q methodology in the context of a cadastre and land registry merger (under one agency) using the Swedish cadastral system as a case study. Precisely, the aim of this paper is to evaluate the effectiveness of Q methodology towards modelling the diverse psychological perceptions of spatial professionals who are in a widely contested decision of merging the cadastre and land registry components of Land administration using the Swedish cadastral system as a case study. An empirical approach that is prescribed by Q methodology starts with the concourse development, followed by the design of statements and q sort instrument, selection of the participants, the q-sorting exercise, factor extraction by PQMethod and finally narrative development by logic of abduction. The paper uses 36 statements developed from a dominant competing value theory that stands out on its reliability and validity, purposively selects 19 participants to do the Qsorting exercise, proceeds with factor extraction from the diversity using varimax rotation and judgemental rotation provided by PQMethod and effect the narrative construction using the logic abduction. The findings from the diverse perceptions from cadastral professionals in the merger decision of land registry and cadastre components in Sweden’s mapping agency (Lantmäteriet) shows that focus is rather inclined on the perfection of the relationship between the legal expertise and technical spatial expertise. There is much emphasis on tradition, loyalty and communication attributes which concern the organisation’s internal environment rather than innovation and market attributes that reveals customer behavior and needs arising from the changing humankind-land needs. It can be concluded that Q methodology offers effective tools that pursues a psychological approach for the evaluation and gradations of the decisions of strategic change through extracting the local perceptions of spatial expertise.

Keywords: cadastre, factor extraction, land administration merger, land registry, q-methodology, rotation

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Authors: Wan Azuati Wan Omar, Selva Rani John Jasudass, Siti Rohaiza Md. Saad

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Introduction & objective: The objectives of this study were to assess patient’s knowledge of appropriate sublingual glyceryl trinitrate (GTN) use as well as to investigate how patients commonly store and carry their sublingual GTN tablets. Methodology: This was a cross-sectional survey, using a validated researcher-administered questionnaire. The study involved cardiac patients receiving sublingual GTN attending the outpatient and inpatient departments of Taiping Hospital, a non-academic public care hospital. The minimum calculated sample size was 92, but 100 patients were conveniently sampled. Respondents were interviewed on 3 areas, including demographic data, knowledge and use of sublingual GTN. Eight items were used to calculate each subject’s knowledge score and six items were used to calculate use score. Results: Of the 96 patients who consented to participate, majority (96.9%) were well aware of the indication of sublingual GTN. With regards to the mechanism of action of sublingual GTN, 73 (76%) patients did not know how the medication works. Majority of the patients (66.7%) knew about the proper storage of the tablet. In relation to the maximum number of sublingual GTN tablets that can be taken during each angina episode, 36.5% did not know that up to 3 tablets of sublingual GTN can be taken during each episode of angina. Fifty four (56.2%) patients were not aware that they need to replace sublingual GTN every 8 weeks after receiving the tablets. Majority (69.8%) of the patients demonstrated lack of knowledge with regards to the use of sublingual GTN as prevention of chest pain. Conclusion: Overall, patients’ knowledge regarding the self administration of sublingual GTN is still inadequate. The findings support the need for more frequent reinforcement of patient education, especially in the areas of preventive use, storage and drug stability.

Keywords: glyceryl trinitrate, knowledge, adherence, patient education

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Authors: Vandana T. Gawande, Kailash G. Bothara, Chandani O. Satija

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The present research work was aimed to determine stability of cefprozil monohydrate (CEFZ) as per various stress degradation conditions recommended by International Conference on Harmonization (ICH) guideline Q1A (R2). Forced degradation studies were carried out for hydrolytic, oxidative, photolytic and thermal stress conditions. The drug was found susceptible for degradation under all stress conditions. Separation was carried out by using High Performance Thin Layer Chromatographic System (HPTLC). Aluminum plates pre-coated with silica gel 60F254 were used as the stationary phase. The mobile phase consisted of ethyl acetate: acetone: methanol: water: glacial acetic acid (7.5:2.5:2.5:1.5:0.5v/v). Densitometric analysis was carried out at 280 nm. The system was found to give compact spot for cefprozil monohydrate (0.45 Rf). The linear regression analysis data showed good linear relationship in the concentration range 200-5.000 ng/band for cefprozil monohydrate. Percent recovery for the drug was found to be in the range of 98.78-101.24. Method was found to be reproducible with % relative standard deviation (%RSD) for intra- and inter-day precision to be < 1.5% over the said concentration range. The method was validated for precision, accuracy, specificity and robustness. The method has been successfully applied in the analysis of drug in tablet dosage form. Three unknown degradation products formed under various stress conditions were isolated by preparative HPTLC and characterized by mass spectroscopic studies.

Keywords: cefprozil monohydrate, degradation products, HPTLC, stress study, stability indicating method

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Authors: Khaled Alshammari

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Ciprofloxacin (CIP) is a common antibiotic drug used as a strudy electron donor that interacts with dynamic π -acceptors such as 2,3-dinitrosalsylic acid (HDNS) and Tetracyanoethylene (TCNE) for synthesizing a new model of charge transfer (CT) complexes. The synthesized complexes were identified using diverse analytical methods such as UV–vis spectra, photometric titration measurements, FT-IR, HNMR Spectroscopy, and thermogravimetric analysis techniques (TGA/DTA). The stoichiometries for all the formed complexes were found to be a 1:1 M ratio between the reactants. The characteristic spectroscopic properties such as transition dipole moment (µ), oscillator strength (f), formation constant (KCT), ionization potential (ID), standard free energy (∆G), and energy of interaction (ECT) for the CT-complexes were collected. The developed CT complexes were tested for their toxicity on main organs, antimicrobial activity, antioxidant activity, and biofilm formation.

Keywords: biological, biofilm, toxicity, thermal analysis, charge transfer, spectroscopy

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Authors: Carol Yue-En Ong, Angelina Hui-Min Tan, Quan Liu, Paul Chi-Lui Ho

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A public general hospital in Singapore has recently implemented an automated unit-dose machine in their inpatient dispensary, Swisslog, with the objective of reducing human error and improving patient safety. However, a concern in stability arises as tablets are removed from their original packaging (bottled loose tablets/capsules) and are repackaged into individual, clear plastic wrappers as unit doses in the system. Drugs that are light-sensitive and hygroscopic would be more susceptible to degradation as the wrapper does not offer full protection. Hence, this study was carried out to study the stability of haloperidol tablets and phenytoin capsules that are light-sensitive and hygroscopic respectively. Validated HPLC-UV assays were first established for quantification of these two compounds. The medications involved were put in the Swisslog and sampled every week for one month. The collected data was analysed and showed no degradation over time. This study also explored an alternative approach for drug stability determination-Raman spectroscopy. The advantage of Raman spectroscopy is its high time efficiency and non-destructive nature. The results suggest that drug degradation can indeed be detected using Raman microscopy, but further research is needed to establish this approach for quantification or qualification of compounds. NanoRam®, a portable Raman spectrocope was also used alongside Raman microscopy but was unsuccessful in detecting degradation in this study.

Keywords: drug stability, haloperidol, HPLC, phenytoin, raman spectroscopy, Swisslog

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Authors: Syed Asif Hassan, Tabrej Khan

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Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

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Authors: Nabil A. Albaser

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Background: There is a serious problem with adverse drug reactions (ADRs) everywhere, including Yemen. Since it helps with the detection, assessment, reporting and prevention of ADRs, pharmacovigilance (PV) is an essential part of the healthcare system. The unbiased reporting of ADRs remains the foundation of PV. Students majoring in healthcare should acquire the knowledge and skills necessary to conduct PV in a range of clinical settings. The primary objective of this study was to evaluate the understanding and attitudes of final-year Pharmacy, Nursing, and Midwifery students at Al-Razi University in Sana'a, Yemen, regarding PV and ADRs reporting. Methods: The study followed descriptive cross-sectional approach. A validated, self-administered questionnaire with three parts—demographic information, knowledge, and perceptions of Pharmacovigilance was online distributed to final-year Pharmacy, Nursing, and Midwifery students. The questionnaire was given to 175 students; 122 of them responded with a percentage (69.7%). Results: The majority of respondents were male (79.5%). More than the tow-third of the students, 68.9%, were beyond the age of 23. Although the majority of students, 80%, heard about the terms of ADRs and PV, but only 50% and 57.4% of the respondents, respectively, could define the both terms correctly. However, only 11.48 % of them, nevertheless, took a PV course. More than a half of them (56.6%) had a positive perceptions towards pharmacovigilance and ADR reporting and had a moderate degree of knowledge (68.9%). Conclusion: The study demonstrated that the participants lacked sufficient knowledge of pharmacovigilance and ADR reporting. They showed a moderate level of understanding of reporting ADRs as well as a favorable opinion of dealing with and reporting ADRs. Yemen's health care curriculum should include lessons on pharmacovigilance.

Keywords: adverse drug reaction reporting, pharmacovigilance, yemen, knowlegde

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Authors: Seolah Lee, Yoohyk Jang, Soyoung Lee, Kon Chu, Sang Kun Lee

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Objective: The International League Against Epilepsy (ILAE) currently suggests a topiramate serum level range of 5-20 mg/L. However, numerous institutions have observed substantial drug response at lower levels. This study aims to investigate the correlation between topiramate serum levels, drug responsiveness, and adverse events to establish a more accurate and tailored therapeutic range. Methods: We retrospectively analyzed topiramate serum samples collected between January 2017 and January 2022 at Seoul National University Hospital. Clinical data, including serum levels, antiseizure regimens, seizure frequency, and adverse events, were collected. Patient responses were categorized as "insufficient" (reduction in seizure frequency <50%) or "sufficient" (reduction ≥ 50%). Within the "sufficient" group, further subdivisions included seizure-free and tolerable seizure subgroups. A population pharmacokinetic model estimated serum levels from spot measurements. ROC curve analysis determined the optimal serum level cut-off. Results: A total of 389 epilepsy patients, with 555 samples, were reviewed, having a mean dose of 178.4±117.9 mg/day and a serum level of 3.9±2.8 mg/L. Out of the samples, only 5.6% (n=31) exhibited insufficient response, with a mean serum level of 3.6±2.5 mg/L. In contrast, 94.4% (n=524) of samples demonstrated sufficient response, with a mean serum level of 4.0±2.8 mg/L. This difference was not statistically significant (p = 0.45). Among the 78 reported adverse events, logistic regression analysis identified a significant association between ataxia and serum concentration (p = 0.04), with an optimal cut-off value of 6.5 mg/L. In the subgroup of patients receiving monotherapy, those in the tolerable seizure group exhibited a significantly higher serum level compared to the seizure-free group (4.8±2.0 mg/L vs 3.4±2.3 mg/L, p < 0.01). Notably, patients in the tolerable seizure group displayed a higher likelihood of progressing into drug-resistant epilepsy during follow-up visits compared to the seizure-free group. Significance: This study proposed an optimal therapeutic concentration for topiramate based on the patient's responsiveness to the drug and the incidence of adverse effects. We employed a population pharmacokinetic model and analyzed topiramate serum levels to recommend a serum level below 6.5 mg/L to mitigate the risk of ataxia-related side effects. Our findings also indicated that topiramate dose elevation is unnecessary for suboptimal responders, as the drug's effectiveness plateaus at minimal doses.

Keywords: topiramate, therapeutic range, low dos, antiseizure effect

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Authors: Paresh M. Patel, Amit A. Patel, R. H. Parikh

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The present investigation was undertaken to fabricate modified transport fluconazole that belongs to BCS class II and have a poor applicability on topical infection. So to improve topical application, transdermal spray could play a vital role by using ethyl cellulose and Eudragit® S100 as film-forming polymers. Concentration of Eudragit® S100, ethyl cellulose and permeation enhancer (camphor and menthol) were selected as independent variables, whereas drying time, viscosity and in-vitro drug release were selected as dependent variables in factorial design. The viscosity, drying time and in-vitro drug release of the optimize batch B15 was 40.1 cps, 47 sec. and 90.79% respectively. The film of optimized batch was flexible and dermal-adhesive.

Keywords: Eudragit, ethyl cellulose, fluconazole, transdermal spray

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Authors: Sahar El Shair, Laura Greco, William Reay, Murray Cairns

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Background: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory, autoimmune disease that involves damages to joints and erosions to the associated bones and cartilage, resulting in reduced physical function and disability. RA is a multifactorial disorder influenced by heterogenous genetic and environmental factors. Whilst different medications have proven successful in reducing inflammation associated with RA, they often come with significant side effects and limited efficacy. To address this, the novel pharmagenic enrichment score (PES) algorithm was tested in self-reported RA patients from the UK Biobank (UKBB), which is a cohort of predominantly European ancestry, and identified individuals with a high genetic risk in clinically actionable biological pathways to identify novel opportunities for precision interventions and drug repurposing to treat RA. Methods and materials: Genetic association data for rheumatoid arthritis was derived from publicly available genome-wide association studies (GWAS) summary statistics (N=97173). The PES framework exploits competitive gene set enrichment to identify pathways that are associated with RA to explore novel treatment opportunities. This data is then integrated into WebGestalt, Drug Interaction database (DGIdb) and DrugBank databases to identify existing compounds with existing use or potential for repurposed use. The PES for each of these candidates was then profiled in individuals with RA in the UKBB (Ncases = 3,719, Ncontrols = 333,160). Results A total of 209 pathways with known drug targets after multiple testing correction were identified. Several pathways, including interferon gamma signaling and TID pathway (which relates to a chaperone that modulates interferon signaling), were significantly associated with self-reported RA in the UKBB when adjusting for age, sex, assessment centre month and location, RA polygenic risk and 10 principal components. These pathways have a major role in RA pathogenesis, including autoimmune attacks against certain citrullinated proteins, synovial inflammation, and bone loss. Encouragingly, many also relate to the mechanism of action of existing RA medications. The analyses also revealed statistically significant association between RA polygenic scores and self-reported RA with individual PES scorings, highlighting the potential utility of the PES algorithm in uncovering additional genetic insights that could aid in the identification of individuals at risk for RA and provide opportunities for more targeted interventions. Conclusions In this study, pharmacologically annotated genetic risk was explored through the PES framework to overcome inter-individual heterogeneity and enable precision drug repurposing in RA. The results showed a statistically significant association between RA polygenic scores and self-reported RA and individual PES scorings for 3,719 RA patients. Interestingly, several enriched PES pathways were targeted by already approved RA drugs. In addition, the analysis revealed genetically supported drug repurposing opportunities for future treatment of RA with a relatively safe profile.

Keywords: rheumatoid arthritis, precision medicine, drug repurposing, system biology, bioinformatics

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Authors: Funmilola O. Omoya, Abdul O. Momoh

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Malaria constitutes one of the major health problems in Nigeria. One of the reasons attributed for the upsurge was the development of resistance of Plasmodium falciparum and the emergence of multi-resistant strains of the parasite to anti-malaria drugs. A continued search for other effective, safe and cheap plant-based anti-malaria agents thus becomes imperative in the face of these difficulties. The objective of this study is therefore to evaluate the in vivo anti-malarial efficacy of ethanolic extracts of Chromolaena odorata and Androgaphis paniculata leaves. The two plants were evaluated for their anti-malaria efficacy in vivo in a 4-day curative test assay against Plasmodium berghei strain in mice. The group treated with 500mg/ml dose of ethanolic extract of A. paniculata plant showed parasite suppression with increase in Packed Cell Volume (PCV) value except day 3 which showed a slight decrease in PCV value. During the 4-day curative test, an increase in the PCV values, weight measurement and zero count of Plasmodium berghei parasite values was recorded after day 3 of drug administration. These results obtained in group treated with A. paniculata extract showed anti-malarial efficacy with higher mortality rate in parasitaemia count when compared with Chromolaena odorata group. These results justify the use of ethanolic extracts of A. paniculata plant as medicinal herb used in folklore medicine in the treatment of malaria.

Keywords: anti-malaria, curative, plant-based anti-malaria agents, biology

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Authors: Swapnila V. Shinde, Hemant P. Joshi, Sumit R. Dhas, Dhananjaysingh B. Rajput

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The objective of the present study is to develop hydro-dynamically balanced system for atenolol, β-blocker as a single unit floating tablet. Atenolol shows pH dependent solubility resulting into a bioavailability of 36%. Thus, site specific oral controlled release floating drug delivery system was developed. Formulation includes novice use of rate controlling polymer such as locust bean gum (LBG) in combination of HPMC K4M and gas generating agent sodium bicarbonate. Tablet was prepared by direct compression method and evaluated for physico-mechanical properties. The statistical method was utilized to optimize the effect of independent variables, namely amount of HPMC K4M, LBG and three dependent responses such as cumulative drug release, floating lag time, floating time. Graphical and mathematical analysis of the results allowed the identification and quantification of the formulation variables influencing the selected responses. To study the gastrointestinal transit of the optimized gastro-retentive formulation, in vivo gamma scintigraphy was carried out in six healthy rabbits, after radio labeling the formulation with 99mTc. The transit profiles demonstrated that the dosage form was retained in the stomach for more than 5 hrs. The study signifies the potential of the developed system for stomach targeted delivery of atenolol with improved bioavailability.

Keywords: floating tablet, factorial design, gamma scintigraphy, antihypertensive model drug, HPMC, locust bean gum

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Authors: Seyran Naghdi

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Background: Orphan drug development is limited by very high costs attributed to the research and development and small size market. How health policymakers address this challenge to consider both supply and demand sides need to be explored for directing the policies and plans in the right way. The price is an important signal for pharmaceutical companies’ profitability and the patients’ accessibility as well. Objective: This study aims to find out the orphan drugs' price-setting patterns and approaches in health systems through a systematic review of the available evidence. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach was used. MedLine, Embase, and Web of Sciences were searched via appropriate search strategies. Through Medical Subject Headings (MeSH), the appropriate terms for pricing were 'cost and cost analysis', and it was 'orphan drug production', and 'orphan drug', for orphan drugs. The critical appraisal was performed by the Joanna-Briggs tool. A Cochrane data extraction form was used to obtain the data about the studies' characteristics, results, and conclusions. Results: Totally, 1,197 records were found. It included 640 hits from Embase, 327 from Web of Sciences, and 230 MedLine. After removing the duplicates, 1,056 studies remained. Of them, 924 studies were removed in the primary screening phase. Of them, 26 studies were included for data extraction. The majority of the studies (>75%) are from developed countries, among them, approximately 80% of the studies are from European countries. Approximately 85% of evidence has been produced in the recent decade. Conclusions: There is a huge variation of price-setting among countries, and this is related to the specific pharmacological market structure and the thresholds that governments want to intervene in the process of pricing. On the other hand, there is some evidence on the availability of spaces to reduce the very high costs of orphan drugs development through an early agreement between pharmacological firms and governments. Further studies need to focus on how the governments could incentivize the companies to agree on providing the drugs at lower prices.

Keywords: orphan drugs, orphan drug production, pricing, costs, cost analysis

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Authors: Parisa Shirzadeh

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Drug delivery systems in which drugs are traditionally used, multi-stage and at specified intervals by patients, do not meet the needs of the world's up-to-date drug delivery. In today's world, we are dealing with a huge number of recombinant peptide and protean drugs and analogues of hormones in the body, most of which are made with genetic engineering techniques. Most of these drugs are used to treat critical diseases such as cancer. Due to the limitations of the traditional method, researchers sought to find ways to solve the problems of the traditional method to a large extent. Following these efforts, controlled drug release systems were introduced, which have many advantages. Using controlled release of the drug in the body, the concentration of the drug is kept at a certain level, and in a short time, it is done at a higher rate. Graphene is a natural material that is biodegradable, non-toxic, and natural compared to carbon nanotubes; its price is lower than carbon nanotubes and is cost-effective for industrialization. On the other hand, the presence of highly effective surfaces and wide surfaces of graphene plates makes it more effective to modify graphene than carbon nanotubes. Graphene oxide is often synthesized using concentrated oxidizers such as sulfuric acid, nitric acid, and potassium permanganate based on Hummer 1 method. In comparison with the initial graphene, the resulting graphene oxide is heavier and has carboxyl, hydroxyl, and epoxy groups. Therefore, graphene oxide is very hydrophilic and easily dissolves in water and creates a stable solution. On the other hand, because the hydroxyl, carboxyl, and epoxy groups created on the surface are highly reactive, they have the ability to work with other functional groups such as amines, esters, polymers, etc. Connect and bring new features to the surface of graphene. In fact, it can be concluded that the creation of hydroxyl groups, Carboxyl, and epoxy and in fact graphene oxidation is the first step and step in creating other functional groups on the surface of graphene. Chitosan is a natural polymer and does not cause toxicity in the body. Due to its chemical structure and having OH and NH groups, it is suitable for binding to graphene oxide and increasing its solubility in aqueous solutions. Graphene oxide (GO) has been modified by chitosan (CS) covalently, developed for control release of doxorubicin (DOX). In this study, GO is produced by the hummer method under acidic conditions. Then, it is chlorinated by oxalyl chloride to increase its reactivity against amine. After that, in the presence of chitosan, the amino reaction was performed to form amide transplantation, and the doxorubicin was connected to the carrier surface by π-π interaction in buffer phosphate. GO, GO-CS, and GO-CS-DOX characterized by FT-IR, RAMAN, TGA, and SEM. The ability to load and release is determined by UV-Visible spectroscopy. The loading result showed a high capacity of DOX absorption (99%) and pH dependence identified as a result of DOX release from GO-CS nanosheet at pH 5.3 and 7.4, which show a fast release rate in acidic conditions.

Keywords: graphene oxide, chitosan, nanosheet, controlled drug release, doxorubicin

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Authors: Jyoti Singh, Ranju Bansal

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Fighting pain and inflammation is a common problem faced by physicians while dealing with a wide variety of diseases. Since ancient time nonsteroidal anti-inflammatory agents (NSAIDs) and opioids have been the cornerstone of treatment therapy, however, the usefulness of both these classes is limited due to severe side effects. NSAIDs, which are mainly used to treat mild to moderate inflammatory pain, induce gastric irritation and nephrotoxicity whereas opioids show an array of adverse reactions such as respiratory depression, sedation, and constipation. Moreover, repeated administration of these drugs induces tolerance to the analgesic effects and physical dependence. Further discovery of selective COX-2 inhibitors (coxibs) suggested safety without any ulcerogenic side effects; however, long-term use of these drugs resulted in kidney and hepatic toxicity along with an increased risk of secondary cardiovascular effects. The basic approaches towards inflammation and pain treatment are constantly changing, and researchers are continuously trying to develop safer and effective anti-inflammatory drug candidates for the treatment of different inflammatory conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, psoriasis and multiple sclerosis. Synthetic 3(2H)-pyridazinones constitute an important scaffold for drug discovery. Structure-activity relationship studies on pyridazinones have shown that attachment of a lactam at N-2 of the pyridazinone ring through a methylene spacer results in significantly increased anti-inflammatory and analgesic properties of the derivatives. Further introduction of the heterocyclic ring at lactam nitrogen results in improvement of biological activities. Keeping in mind these SAR studies, a new series of compounds were synthesized as shown in scheme 1 and investigated for anti-inflammatory, analgesic, anti-platelet activities and docking studies. The structures of newly synthesized compounds have been established by various spectroscopic techniques. All the synthesized pyridazinone derivatives exhibited potent anti-inflammatory and analgesic activity. Homoveratryl substituted derivative was found to possess highest anti-inflammatory and analgesic activity displaying 73.60 % inhibition of edema at 40 mg/kg with no ulcerogenic activity when compared to standard drugs indomethacin. Moreover, 2-substituted-4-benzo[d][1,3]dioxole-6-phenylpyridazin-3(2H)-ones derivatives did not produce significant changes in bleeding time and emerged as safe agents. Molecular docking studies also illustrated good binding interactions at the active site of the cyclooxygenase-2 (hCox-2) enzyme.

Keywords: anti-inflammatory, analgesic, pyridazin-3(2H)-one, selective COX-2 inhibitors

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Authors: Alba Luna Jimenez, Maria Dolores Hernando

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The administration of veterinary treatments at higher doses than the recommended Varroa mite control in beehive matrices has the potential to generate residues in the honeybee colony and in the derived products for consumption. Honeybee colonies can also be indirectly exposed to residues of plant protection products when foraging in crops, wildflowers near the crops, or in urban gardens just after spraying. The study evaluates the presence of both types of residues, veterinary treatments, and pesticides in beeswax, bee bread, and honey. The study was carried out in apiaries located in agricultural zones and forest areas in Andalusia, Spain. Up to nineteen residues were identified above LOQ using gas chromatography-triple quadrupole-mass spectrometry analysis (GC-MS/MS). Samples were extracted by a modified QuEChERs method. Chlorfenvinphos was detected in beeswax and bee bread despite its use is not authorized for Varroa mite control. Residues of fluvalinate-tau, authorized as veterinary treatment, were detected in most of the samples of beeswax and bee bread, presumably due to overdose or also to its potential for accumulation associated with its marked liposolubility. Residues of plant protection products were also detected in samples of beeswax and bee bread. Pesticide residues were detected above the LOQ that was established at 5 µg.kg⁻¹, which is the minimum concentration that can be quantified with acceptable accuracy and precision, as described in the European guidelines for pesticide residue analysis SANTE/11945/2015. No residues of phytosanitary treatments used in agriculture were detected in honey.

Keywords: honeybee colony, mass spectrometry analysis, pesticide residues, Varroa destructor, veterinary treatment

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