Stability of N-Acetylcysteine 60 mg/mL in Extemporaneously Compounded Injectable Solutions

Background: N-Acetylcysteine (NAC) administered by the IV route is the current treatment of choice for acetaminophen overdose. However, the protocol approved by health authorities in most countries has a complex dosing regimen, which leads to dosage errors in one-third of cases. Therefore, the Canadian Antidote Guide in Acute Care Toxicology and individual poison centres have begun to recommend a simplified regimen using continuous IV infusion. Unfortunately, no study has demonstrated the stability of IV solutions of NAC at concentrations above 30 mg/mL or in solutions other than 5% dextrose. Objective: To evaluate the stability of solutions of NAC 60 mg/mL in 0.9% sodium chloride, 0.45% sodium chloride, or 5% dextrose, stored for up to 72 hours in polyvinyl chloride (PVC) bags at 25°C. Methods: Solutions of the desired concentration were prepared from a commercial solution of NAC 200 mg/mL, with dilution in 0.9% sodium chloride, 0.45% sodium chloride, or 5% dextrose, and were then stored at room temperature in PVC bags for up to 72 hours. At predetermined time points (0, 16, 24, 40, 48 and 72 h), samples were collected and analyzed using a stability-indicating high-performance liquid chromatography method. A solution was considered stable if it maintained at least 90.0% of its initial concentration. Particulate matter count was also evaluated to confirm chemical stability. Finally, organoleptic properties, such as odour and colour, were evaluated to assess the stability of the solutions. Results: All solutions maintained at least 98.7% of their initial concentration. No obvious changes in odour or colour were observed. Moreover, particle counts remained acceptable throughout the study, according to the criteria specified in United States Pharmacopeia (USP) General Chapter <788>. Conclusions: NAC 60 mg/mL, diluted in 0.9% sodium chloride, 0.45% sodium chloride, or 5% dextrose and stored in PVC bags at 25°C, was chemically and physically stable for a period of at least 72 hours. RÉSUMÉ Contexte : La N-acétylcystéine (NAC) administrée par IV est actuellement le traitement de choix en cas de surdose d’acétaminophène. Cependant, le protocole approuvé par les autorités sanitaires de la plupart des pays s’accompagne d’un schéma posologique complexe qui entraîne des erreurs de dosage dans un tiers des cas. C’est pourquoi, le Guide canadien des antidotes en toxicologie d’urgence et les centres antipoison ont commencé à recommander un schéma simplifié utilisant des perfusions IV. Malheureusement, aucune étude n’a permis de démontrer la stabilité des solutions IV de NAC à des concentrations supérieures à 30 mg/mL ou dans des solutions autres que 5 % de dextrose. Objectif : Évaluer la stabilité des solutions de 60 mg/mL de NAC dans 0,9 % de chlorure de sodium, 0,45 % de chlorure de sodium ou 5 % de dextrose, stockées jusqu’à 72 heures dans des pochettes de chlorure de polyvinyle (PVC) à 25 °C. Méthodes : Les solutions ont été préparées à partir d’une solution commerciale de 200 mg/mL de NAC, avec une dilution dans 0,9 % de chlorure de sodium, dans 0,45 % de chlorure de sodium ou dans 5 % de dextrose. Elles ont ensuite été stockées à température ambiante dans des pochettes en PVC pendant une période allant jusqu’à 72 h. À des instants prédéterminés (0, 16, 24, 40, 48 et 72 h), des échantillons étaient recueillis et analysés à l’aide d’une méthode de chromatographie en phase liquide à haute performance indiquant la stabilité. Si la solution préservait au moins 90 % de sa concentration initiale, elle était jugée stable. Un comptage de particules a aussi permis de confirmer la stabilité chimique. Finalement, les propriétés organoleptiques, comme l’odeur et la couleur, ont été examinées pour évaluer la stabilité des solutions de NAC. Résultats : Toutes les solutions préservaient au moins 98,7 % de leur concentration initiale. Aucun changement manifeste d’odeur ou de couleur n’a été observé. De plus, le nombre de particules est resté acceptable pendant toute la durée de l’étude selon les critères indiqués dans le chapitre général de la Pharmacopée américaine (USP) <788>. Conclusions : La solution de 60 mg/mL de NAC, diluée dans 0,9 % de chlorure de sodium, dans 0,45 % de chlorure de sodium ou dans 5 % de dextrose et stockée dans des pochettes en PVC à 25 °C était chimiquement et physiquement stable pendant au moins 72 h.

Creation of a regional hazardous drug handling task force

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose A regional task force of health-system pharmacy leaders was created to assist with successful adoption of United States Pharmacopeia (USP) general chapter &lt;800&gt;. Summary A group of pharmacy leaders in the Kansas City region identified potential benefits to healthcare personnel and patients if hazardous drug handling procedures were standardized. A task force was created, a preimplementation survey was distributed, and meetings were held monthly to discuss sections of USP &lt;800&gt; identified as the most challenging to implement. The task force focused on an assessment of risk tool, hot topics, cleanroom design, and a detailed analysis of controversial medications. After the first year of meetings, a postimplementation survey was distributed, and the results were analyzed. The task force created significant value for the participants and achieved the goal of facilitating efficient USP &lt;800&gt; implementation resulting in greater compliance and consistency across the multiple health systems represented. Over 5,100 beds and 200 clinic sites were affected by this task force’s efforts. Nearly three-fourths (73%) of respondents reported that the task force was “extremely helpful,” and the majority (64%) of respondents adopted most or all (81%-100%) of the task force’s assessment of risk choices. Prioritization of tasks, information sharing, and decision-making were areas where the individual leaders were most supported. Conclusion Creating a structure to eliminate barriers and facilitate collaboration among regional pharmacy leaders provided a framework for successful implementation of USP &lt;800&gt; requirements. This interdependent leadership model produced innovative and standardized solutions and should be considered when addressing complicated initiatives that impact the profession.

PROTO-HEGUMEN JOSAPHAT OHOTSKYJ’S CIRCULAR LETTER (30.11.1784)

Summary. The purpose of this study is to analyze the information content of the circular, highlighting the main thematic parts. Research methodology is based on the use of analytical and synthetic critique of the sources. To establish the objectivity of information, in the absence of the original letter, its content is compared with other handwritten copies and old printed copies which we found. The scientific novelty is seen in the fact that for the first time Proto-hegumen Josaphat Ohotskyj’s circular received a wide public access. Conclusions. The mentioned circular reflects the multilevel system of management of Basilian monasteries: the Apostolic See, the provincial chapter and the council. After all, in the period under consideration, the Basilian Order already held papal law. The Pope reserved the right to approve the decrees of the general chapters, making changes and additions to them. The provincial chapters considered issues not only related to the election of the provincial council, but also resolutions on the regulation of the ascetic structure of the monks, their spiritual and intellectual formation and the financial and property status of the monasteries. These decrees were based on the particular law of the Basilian Order according to which the provincial chapter was endowed not only with elective but also with legislative functions that were limited by territorial boundaries. Given the dispersion of the Basilian monasteries due to the first division of the Commonwealth, there was a political difficulty in convening a general chapter, as secular autocrats forbade monks to move outside the empires. Secular rulers demanded that the Basilian monastics form autocratic governing bodies for monasteries located within individual states. In such socio-political conditions, the importance of the provincial chapter and the council is growing.

Implementation and validation of an in-house combined fluorescein/media-fill test to qualify radiopharmacy operators

Background The purpose of this work was to design, validate and implement a media-fill test combined with fluorescein (MFT-F) for the specific qualification and training of radiopharmacy operators, in accordance with United States Pharmacopeia General Chapter 797 and European Good Manufacturing Practices. MFT-F was embedded in the quality management system of our radiopharmacy unit. Its validation involved fluorescein concentration choice, media growth promotion test and evaluation protocol controls (with or without intentional aseptic mistakes). Each operator was evaluated following a three-part evaluation form. Evaluation criteria related to garbing and hygiene, fluorescent contamination and bacteriological contamination (pre- and post-evaluation environment controls and MFT-F samples). Combined MFT-F allowed the assessment of aseptic compounding skills and non-contamination of the working area through a single evaluation. It was also designed to fit the constraints of radiopharmacy common practice related to radiation protection equipment and to the small volumes handled. Results A 0.01% fluorescein concentration was chosen to prepare MFT-F. Addition of fluorescein in the culture medium did not jeopardize its growth properties according to growth promotion test. Eleven operators were evaluated and carried out 3 MFT-F over 3 successive days. Pre- and post-evaluation bacteriological controls of every session showed no CFU of microbiological contaminant above 5. All operators validated the garbing and hygiene evaluation, with an average score of 92.7%. All operators validated the fluorescent contamination evaluation, with an average score of 29.4 out of 30. None of the MFT-F samples showed any visible bacterial growth after incubation. Conclusions Combined MFT-F, as a part of a comprehensive sterile compounding training program, appeared as a convenient and promising tool to increase both the sterile compounding safety and awareness of radioactive contamination in radiopharmacy.

Small talk and large impact: the importance of small RNA molecules in the fight against plant diseases.

This short and general chapter summarizes how plants and pathogens communicate using not only proteins for recognition and signal transduction or other metabolites but also RNA molecules where small RNAs with sizes between 21 to 40 nt are most important. These small RNAs can move between plants and a range of interacting pathogenic organisms in both directions, that is, a 'cross-kingdom' communication process. The first reports on RNA-based communications between plants and plant pathogenic fungi appeared about 10 years ago. Since that time, we have learnt much about sRNA biology in plants and their function in different parasitic organisms. However, many questions on the processes involved remain unanswered. Such information is crucial in order to sustain high crop production. Besides giving a brief background, we highlight the interactions between the potato late blight pathogen and its plant host potato.

Small talk and large impact: the importance of small RNA molecules in the fight against plant diseases.

This short and general chapter summarizes how plants and pathogens communicate using not only proteins for recognition and signal transduction or other metabolites but also RNA molecules where small RNAs with sizes between 21 to 40 nt are most important. These small RNAs can move between plants and a range of interacting pathogenic organisms in both directions, that is, a 'cross-kingdom' communication process. The first reports on RNA-based communications between plants and plant pathogenic fungi appeared about 10 years ago. Since that time, we have learnt much about sRNA biology in plants and their function in different parasitic organisms. However, many questions on the processes involved remain unanswered. Such information is crucial in order to sustain high crop production. Besides giving a brief background, we highlight the interactions between the potato late blight pathogen and its plant host potato.

A course of Elementary Probability Course

This book introduces to the theory of probabilities from the beginning. Assuming that the reader possesses the normal mathematical level acquired at the end of the secondary school, we aim to equip him with a solid basis in probability theory. The theory is preceded by a general chapter on counting methods. Then, the theory of probabilities is presented in a discrete framework. Two objectives are sought. The first is to give the reader the ability to solve a large number of problems related to probability theory, including application problems in a variety of disciplines. The second is to prepare the reader before he takes course on the mathematical foundations of probability theory. In this later book, the reader will concentrate more on mathematical concepts, while in the present text, experimental frameworks are mostly found. If both objectives are met, the reader will have already acquired a definitive experience in problem-solving ability with the tools of probability theory and at the same time he is ready to move on to a theoretical course on probability theory based on the theory of Measure and Integration. The book ends with a chapter that allows the reader to begin an intermediate course in mathematical statistics.