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The treatment of several pediatric metabolic diseases involves vitamins supplementation. Among these, thiamine, riboflavin, pyridoxine and biotin can be prescribed and compounded as hard gelatin capsules. In compounding practice, a medication can be done extemporaneously, leading to a risk of error. However, a medication can also be done in advance, analytically controlled and stored. Such practice reduce the risk of error and decrease the cost, but also imposes the realization of stability studies to establish beyond-use-dates. Thiamine hydrochloride, riboflavin, pyridoxine hydrochloride, and biotin hard gelatin capsules chromatographic and microbiological methods were both validated and used to perform stability studies. Thiamine hydrochloride 50 mg hard gelatin capsules with microcrystalline cellulose and silica as excipients are stable for 6 months when stored at 25 ° C/ 60% RH protected from light. Riboflavin 50 mg with microcrystalline cellulose, pyridoxine hydrochloride 50 mg with microcrystalline cellulose and biotin 40 mg with microcrystalline cellulose/silica are stable for one year when stored at 25 ° C/ 60% RH protected from light. These results allow the compounding in advance of batches of 300 capsules controlled, stored, and quickly dispensed in case of an emergency, such decreasing the risk of error and/or iatrogenic event.

Erythromycin is a macrolide antibiotic that is also prescribed off-label in premature neonates as a prokinetic agent. There is no oral formulation with dosage and/or excipients adapted for these high-risk patients. Clinical studies of erythromycin as a prokinetic agent were reviewed. Capsules of 20 milligrams of erythromycin were compounded with microcrystalline cellulose. Erythromycin capsules were analyzed using the chromatographic method described in the United States Pharmacopoeia which was found to be stability-indicating. The stability of 20 mg erythromycin capsules stored protected from light at room temperature was studied for one year. 20 mg erythromycin capsules have a beyond use date not lower than one year. 20 milligrams erythromycin capsules can be compounded in batches of 300 unities in hospital pharmacy with a beyond-use-date of one year at ambient temperature protected from light.

In pediatric practice, nalbuphine hydrochloride can be administered by continuous infusion through a multiport manifold or Y-site connection over 24 h in a 60 mL polypropylene syringe unprotected from light at concentrations ranging from 52.1 µg.mL -1 to 333.3 µg.mL -1 in normal saline (NS). To limit the need for multiple injections, nalbuphine hydrochloride may be co-administered with other drugs. Its stability and compatibility were already studied at concentration ranges equal or higher than 1.0 mg.mL -1 . However, when nalbuphine hydrochloride needs to be diluted for a pediatric administration its stability in NS over 24 h of light exposure at ambient temperature and its compatibility with other drugs have never been studied before. A novel chromatographic method using high-performance liquid chromatography (HPLC) was validated by the International Council for Harmonisation (ICH) Q2 (R1) guidelines. The stability of nalbuphine hydrochloride and the appearance of degradation products under five experimental conditions (light, heat, oxidation, basicity, and acidity) were monitored by HPLC-UV for 24 h at ambient temperature at three concentrations administered in pediatric departments (52.1 µg.mL -1 , 166.7 µg.mL -1 and 333.3 µg.mL -1 ). The physical compatibility of nalbuphine hydrochloride with 1:1 (v/v) mixtures of selected drugs used in pediatrics was evaluated by visual inspection and with a 10 µm and 25 µm sub-visible particle counter. Our nalbuphine hydrochloride quantification method has been validated and was stability-indicating. The stability of nalbuphine hydrochloride and the forced degradation assay (light, heat, oxidation, basicity, and acidity) studied for the three concentrations of nalbuphine hydrochloride diluted in 48 mL of NS and stored in a 60 mL polypropylene syringe unprotected from light were compliant for at least 24 h at ambient temperature. Nalbuphine hydrochloride in NS was found to be compatible with several drugs, but was incompatible with furosemide and amphotericin B. Nalbuphine hydrochloride can be administered in pediatric practice using a syringe pump for 24 h. However, drug-drug incompatibilities need to be considered when it is administered through a multiport manifold or Y-site connection.

Environmental monitoring is usually conducted by surface sampling to detect and quantify the presence of cytotoxic drugs after their reconstitution and administration. This technique reveals the origins of residual contamination and is an important component in order to protect healthcare workers from the potential risk of occupational exposure. The aim of this work is to compare various techniques and results of surface sampling for cytotoxics. For each technique, sample processing methods and their analysis were compared from literature data. Sampling is often performed by the wiping technique. After treatment, various single or multicompound technical analyses are used, in particular liquid or gas chromatography involving different detection methods: ultraviolet, mass spectrometry, plasma torch, and voltammetry. Some methods are validated to ensure reliability. Despite published guidelines and the use of isolator technology for the preparation of cytotoxic drugs, workplace contamination persists, leading to chemotherapeutic agents’ exposure of healthcare workers. Efforts need to be maintained with particular emphasis on harmonization and on determining alert level for cytotoxic contamination.

Leishmaniasis, a protozoan disease affecting humans, exposes significant shortcomings in current treatments. In continuation to our previous findings on amidoxime-based antileishmanial compounds bearing a 4,5-dihydrofuran scaffold, twelve new amidoxime derivatives substituted at position 3 with an amide bearing a nitrogen heterocycle were synthesized. This series was designed to replace the sulfone and aryl group on a previously reported HIT. The synthesis of these compounds involved the following three-step pathway: manganese (III) acetate-based cyclization of a β-ketoester, followed by amidation with LiHMDS and a final reaction with hydroxylamine. Three of them, containing either bromine, chlorine, or methyl substitutions and featuring a pyridine moiety, showed an interesting toxicity–activity relationship in vitro. They exhibited IC50 values of 15.0 µM, 16.0 µM, and 17.0 µM against the promastigote form of the parasite and IC50 values of 0.5 µM, 0.6 µM, and 0.3 µM against the intracellular amastigote form, respectively. A selectivity index (SI) greater than 300 was established between the cytotoxic concentrations (in murine macrophages) and the effective concentrations (against the intracellular form of Leishmania amazonensis). This SI is at least seventy times higher than that observed for Pentamidine and twenty-five times higher than that observed for the reference HIT, as previously reported.

Anthracycline antibiotics play an important role in cancer chemotherapy. The need to improve their therapeutic index has stimulated an ongoing search for anthracycline analogs with enhanced properties. This review aims to summarize the common synthetic approaches to benzo[g]quinoxaline-5,10-diones and their uses in heterocyclic chemistry. Because of the valuable biological activities of the 1,4-diazaanthraquinone compounds, a summary of the most promising heterocyclic quinones is provided together with their antitumor properties.

Plasmodium falciparum is a fast-evolving parasite responsible for the fatal disease malaria, making it crucial to renew our therapeutic arsenal. Modulating the artemisinin’s endoperoxide pharmacophore is a promising route to synthesizing new antimalarial derivatives. For the first step of our 20 mmol scale synthesis, catalyzed by manganese (III) acetylacetonate, we applied the conditions previously described in the literature to one of our low-yielding asymmetrically disubstituted alkenes, (2-methylallyl)benzene. Under conditions designed for alkyl derivatives, manganese (II) and (III) acetate catalyzed its peroxycyclization with methyl 3-oxobutanoate to a 1,2-dioxane ring in the presence of oxygen from air at room temperature with a 36% yield, while an oxygen atmosphere, as described in the literature, decreased the yield to 7%. Finally, under conditions designed for aryl derivatives, the yield was reduced to 30%, showing that methylallyl derivatives have an intermediate reactivity that needs further optimization to produce 1,2-dioxane ring by manganese catalyzation in good yields. This work characterizes the product obtained and discusses the most suitable reaction conditions.

Background/Objective: Little information is available on the stability and quality controls of compounded 40% dextrose gel required to ensure its safe use in the treatment and prevention of neonatal hypoglycemia. Whether its efficacy relies on buccal absorption also remains uncertain. This study investigates the stability, microbiological safety, rheological properties and dextrose diffusion of a compounded 40% oral dextrose gel, ensuring it can be widely compounded and stored for clinical use. Methods: A 40% dextrose gel compounded with anhydrous dextrose, carboxymethylcellulose, citric acid, sorbic acid and sterile water was subjected to quality control measures including a dextrose content assay, degradation product analysis, microbiological testing and preservative efficacy. Stability studies were conducted at refrigerated (4–8 °C) and ambient temperatures for 7 days and 3 months, respectively. Rheological properties were assessed, and dextrose permeation was measured through an artificial membrane model that mimics a biological membrane. Results: The compounded gel demonstrated stability for up to 7 days at ambient temperature and 90 days when refrigerated. The dextrose content remained within the acceptable range (90–110%) and microbiological tests confirmed compliance with safety standards. The gel exhibited the consistent rheological properties and shear-thinning behavior appropriate for oral mucosal administration. In vitro permeation studies showed no evidence of dextrose diffusion with a long lag time followed by a low steady-state permeation flux. Conclusions: This study validates the compounding process of a stable 40% oral dextrose gel formulation for neonatal hypoglycemia management, which meets quality control criteria and can be safely administered in clinical practice, offering a cost-effective and safe alternative for neonatal care.

Thoracic malignancies are the main cause of cancer-related deaths worldwide. The need to develop new therapies is therefore urgent. The recognition of new potential therapeutic targets in thoracic malignancies has prompted the development of a number of antibody–drug conjugates. This new class of potent anticancer agents is supposed to more specifically and directly target the tumor while limiting toxicity for healthy tissues by delivering a toxic payload to tumor cells that are recognized by the presence of specific cell surface antigens. Progress in the development of antibody–drug conjugates over the last decade has been significant, with several promising advances. Unfortunately, many failures have also been encountered, often because of unexpectedly severe toxicities that contradicted the assumed mechanism of action, and major challenges remain. Various techniques to reduce the toxicities associated with antibody–drug conjugates are being studied, and the panorama of antibody–drug conjugates in clinical stages continues to increase and evolve. Current efforts in the conjugation and linker chemistries could result in the successful construction of clinically effective compounds. The future clinical development of antibody–drug conjugates could benefit from the identification of such payloads that can provide more safe and effective derivatives. Highly potent compounds with reasonable aqueous solubility, non-immunogenic profile, and stability in storage and the bloodstream should be important aspects of research into cytotoxic payloads.

As part of our ongoing attempt to broaden the applications of the amidoxime moiety as a potential source of new antileishmanial agents, this study focuses on the product 4-(5-Benzyl-3-((4-fluorophenyl)sulfonyl)-5-methyl-4,5-dihydrofuran-2-yl)-2-nitrobenzamide. This unexpected amide was obtained in an 85% yield as the major product with a conventional amidoxime synthesis protocol (Ethanol/Na2CO3) involving the reaction of hydroxylamine and a nitrile group. The formation of this amide derivative instead of the expected amidoxime can be attributed to two complementary effects: the strong electron effect of the nitro group and the influence of ethanol, a polar protic solvent. Alternatively, the desired amidoxime derivative, 4-(5-benzyl-3-((4-fluorophenyl)sulfonyl)-5-methyl-4,5-dihydrofuran-2-yl)-N′-hydroxy-2-nitrobenzimidamide, was obtained in an 80% yield by an alternative protocol (DMSO/KOtBu). This original compound, featuring a nitro group in the ortho position to the amidoxime, will be further evaluated, both in the field of medicinal chemistry and in other relevant areas, highlighting an unusual method to access amidoximes from hindered substrates.