Crystal data CI4HI3N3Mo Ka radiation Mr = 223.28 A = 0.71073,4, AbstractIn the title compound, (-)-cis-3-acetyl-2,2-dimethylcyclobutanecarboxylic acid, C9HI403, carboxyl-toketone chains (catemers) are formed between screwrelated molecules spiraling along the b cell axis, with an O--H...O distance of 2.747 (3)A. The carboxyl C=:O Acta Co'stallographica Section C

A novel set of N-alkyl naphthyridone compounds has been prepared and characterized.These compounds have been compared to analogous 9-acridinones for a possible trypanocidal activity. With reference to this, naphthyridones seem to be more promising compounds than the 9-acridinone ones. INTRODUCTIONWithin the scope of the search of new trypanocidal agents (1-3) we have recently prepared and tested some 1,4-dimethoxy-9-(10H)-acridinone derivatives (4). As the naphtyridine nucleus is structurally related to the acridine one, we were also interested in preparing and investigating antiparasitic activity of some new benzo [b][1,8]-5-naphthyridone derivatives, substituted similarly as acridinones already tested. EXPERIMENTAL Synthesis, trypanocidal activity and DNA binding of new benzo [b] [ 1,8]-naphthyridones derivatives -ChemistryMelting points were determined in open capillary tubes on a Buchi-Tottoli apparatus and are given uncorrected. NMR spectra were recorded at 20.00 ± 0.1 °C, using a Bruker AM 200 spectrometer. Microanalyses were carried out using a Technicon CHN autoanalyzer.G6n6ral procedure for synthesis of compounds 1-8 (scheme 1) Procedure for compounds land 2.A mixture of freshly distilled aniline or properly substituted anilines (80 mmol), 2-chloro nicotonic acid (80 mmol), copper (0.8 g) and xylene (200 ml) is refluxed for 24 h with stirring.After filtration, the mixture is allowed to cool to room temperature. The precipitate obtained is recrystallized. Procedure for compounds 2_and_4Anthranilic acids 1 or 2 (10 mmol) are refluxed for 4 h with polyphosphoric acid in excess (more than 20 fold the weight of anthranilic acid). Then, the mixture is poured on ice and ammonia is slowly added. The precipitate obtained is recrystallized. Procedure for compounds 5 and_£A mixture of naphthyridone 2 or 4 (10 mmol), alkylating agent (15 mmol), and triethylbenzylammonium chloride hydrochloride (5 mmol), aqueous 50 % potassium hydroxide (50 ml), and toluene (100 ml) is refluxed for 24 h with stirring. Then, the organic layer is separated, washed with water, and dried with anhydrous sodium sulfate. After evaporation of solvent, crude product is recrystallized.Procedure for compound Ζ A mixture of £ (2 mmol) and 40 % hydrobromic acid (320 mmol), is refluxed for 4 h with stirring before being allowed to cool to room temperature. Solution is then neutralized with ammonia, with cooling to maintain the temperature at 0° C. The precipitate obtained is recrystallized.

Objective: To determine the incidence and frequency of adverse drug reactions (ADRs) induced by cancer chemotherapy in pediatric inpatients. Patients and methods: This was a six-month prospective observational study in the pediatric hematology-oncology department of the children's hospital of Rabat. This study took into account ADRs manifested by in inpatient children and undergoing cancer chemotherapy. A modified version of the Moroccan Poison Control and Pharmacovigilance Centre's notification form was used to collect demographic, clinical, cancer treatment and ADR-related data. The causality, severity and preventability were assessed for each adverse event. Results: 106 patients out of 118 followed have developed a total of 266 ADRs. The most frequent ADRs were anemia (14.3%), infections (9.4%), leukopenia (8.6%) and fever (8.3%). Vincristine (16.3%), etoposide (14%) and cytarabine (13%) were the most frequently administered products. Cytarabine followed by etoposide were the drugs most involved in ADRs. The majority of ADRs (55.6%) were probable according to the WHO method of causality assessment. Conclusion: Cancer chemotherapy is associated with a high risk of developing ADRs, particularly hematological ADRs in children. Pediatric patients receiving cytarabine and daunorubicin combinations and regimens including anthracyclines should receive more attention. Risk management plans need to be implemented by health care teams in this area.

Introduction A few years after the discovery and development of anti-infectives, this therapeutic feat gave way to bacterial resistance because of the overconsumption of antibiotics, most often with unjustified prescriptions. The objective was to evaluate the compliance of the prescription of antibiotherapy in the pediatric onco-hematology unit of Rabat Children's Hospital and to determine the drug interactions. Material and methods This is a retrospective study of anti-infectives prescriptions in pediatric onco-hematology. All prescriptions containing an antibiotic or antimycotic were isolated at the end of each month for analysis according to the ANSM standard. The variables of compliance analyzed in the prescriptions were: form, indication, posology, duration of the treatment, drug interactions and number of antibiotics which were prescribed. Results The prescriptions containing at least one anti-infective were 195. All the prescriptions were in conformity with their indications; 111 (57%) of the cases were conform with respect to all criteria; 20 (12%) prescriptions were not conform in their form, 12 (6.6%) contained at least one over-dosed drug and 52 (26.7%) contained at least one under-dosed drug. A drug interaction was found in 15 (7.7%) of cases, of which 12 (6.2%) are precautions for use. A drug interaction is present in 1(6,7%) cases when a single antibiotic is prescribed against 3 (20%) cases when 4 antibiotics are prescribed. ( p = 0.007). Conclusion The number of non-compliances in our study was high. It would therefore be advisable to recommend the establishment of an information system to minimize the non-compliances and to ensure a training program for young doctors on international recommendations.

Introduction There is a need for an economic evaluation of the use of closed system (CSTD) in chemotherapy compounding, especially in resource-constrained settings. Objective The objective of this study was to assess the cost saving of the management of cancer drug leftovers before and after introduction of CSTD associated with an extension of the beyond-use date (BUD) of cancer vials. A secondary objective was to estimate the level of minimization of drug wastage. Materials and methods This was a prospective, single-center study with two periods of two months each. The cost of drugs saved by using conventional systems (syringe and needle) without a closed system in the first period was compared to the cost of drugs saved by using the CSTD Chemoclave® system in the second period. The drug waste minimization rate compared actual drug waste to potential waste in Period 2. Results In Period 1, the amount of drug saved accounted for an average of 10.3% of the amount used in milligrams and the amount of drug wasted accounted for an average of 18.7%. In period 2, these proportions were 15.2% and 6.4% respectively. The CSTD generated an extra cost of 11,962.5 USD compared to the conventional system. The drug saved cost related only to the CSTD and the acquisition cost of the CSTD was a deficit of -7,444.95 USD and the cost saved from the compounding (CSTD and syringes) was a gain of 1,722.01 USD. The waste minimization represented an average of 72.5% ± 24.4% of potential waste. Conclusion The use of CSTD to extend the BUD allowed to reduce waste due to microbiological instability without adding an economic profit.

In clinical treatment, the analytical quality assessment of the delivery of chemotherapeutic preparations is required to guarantee the patient’s safety regarding the dose and most importantly the appropriate anticancer drug. On its own, the development of rapid analytical methods allowing both qualitative and quantitative control of the formulation of prepared solutions could significantly enhance the hospital’s workflow, reducing costs, and potentially providing optimal patient care. UV-visible spectroscopy is a nondestructive, fast, and economical technique for molecular characterization of samples. A discrimination and quantification study of three chemotherapeutic drugs doxorubicin, daunorubicin, and epirubicin was conducted, using clinically relevant concentration ranges prepared in 0.9% NaCl solutions. The application of the partial least square discriminant analysis PLS-DA method on the UV-visible spectral data shows a perfect discrimination of the three drugs with a sensitivity and specificity of 100%. The use of partial least square regression PLS shows high quantification performance of these molecules in solution represented by the low value of root mean square error of calibration (RMSEC) and root mean square error of cross validation (RMSCECV) on the one hand and the high value of R -square on the other hand. This study demonstrated the viability of UV-visible fingerprinting (routine approach) coupled with chemometric tools for the classification and quantification of chemotherapeutic drugs during clinical preparation.

BackgroundThe closed system is designed, first, to protect patients and clinicians against exposure to hazardous drugs during the preparation of cytotoxic drugs and secondly, to protect the drugs against any exposure to external microbiological and physical contaminants.PurposeThe aim of this study was to determine the dead volume of spike–connector–syringe system used for the reconstitution of cytotoxic drugs and its impact on the variation of prepared doses.Material and methodsThe spike, connector and syringe (10 or 20 mL) were weighed using an analytical balance before and after passing a solution of distilled water. Taking into account the density of water, we can thus determine the dead volume remaining in every material. For each measurement, the test was performed 30 times for each medical device.ResultsThe table shows that the dead volumes were different for the three devices: spike, connector and syringes (p<0.001). There was no significant differences between the dead volumes of the two syringes tested (10 and 20 mL) (p> 0.05). Dead volume Vial adapter (spike) Connector Syringe 10 mL Syringe 20 mL Mean (mL)0.11920.20430.07020.0596ConclusionReconstitution of cytotoxic drugs is influenced by several factors, some of which are controllable and others are unpredictable. The dead volumes can cause overdose or underdose, especially for preparations of low volume and expensive drugs. This phenomenon is important for connectors and spikes where the dead volume is about 0.2 mL and 0.1 mL, respectively. For syringes, the dead volume is not very important and does not vary with the volume of the syringe. This study showed that we must take into account the dead volume on reconstitution of cytotoxic drugs. Thus it would be highly advisable to use connectors whose dead volume is negligible compared with the prepared final volume.References and/or acknowledgementsAcknowledgements to the analytical chemistry team.No conflict of interest

BackgroundAntacids are intended to neutralise the gastric H+ ions without interfering with the secretory process. They are generally administered 1 h 30 min after the beginning of a meal.Given the multitude of antacids on the market, it would be interesting to have quantitative techniques to compare these products and to demonstrate their physiological behaviour.PurposeTo evaluate the behaviour of antacids in the presence of an increasing amount of acidity in vitro and to predict their use depending on the importance and periodicity of gastric acidity in vivo.Material and methodsWe studied the in vitro behaviour of six antacid drugs. For this, a therapeutic dose was diluted in 100 ml of distilled water, to which were added increasing amounts of 0.1 N HCl in increments of 0.2 ml every 30 s up to a total acid volume of 25 ml. The variation in pH of the mixture was followed by pH-metry. Each test was repeated three times.The composition of the studied antacids is shown in table 1.Abstract DI-071 Table 1Drug AFor 100 ml of oral suspension:-Aluminium hydroxide (3.49 mg)-Magnesium hydroxide (3.99 mg)Drug BFor a 20 g sachet of oral suspension:-Aluminum phosphate gel at 20% (12.38 g)-Magnesium oxide (152 mg)Drug CFor a 20 g sachet of oral suspension:-Colloidal aluminum phosphate at 17% (14.4 g)Drug DFor a 10 ml sachet of oral suspension:-Aluminium alginate (500 mg)-Sodium bicarbonate (267 mg)Drug EFor one effervescent tablet:-Sodium bicarbonate (170 mg)-Sodium sulfate (285 mg)-Sodium dihydrogen phosphate (195 mg)Drug FFor one suckable tablet:-Calcium carbonate (680 mg)-Magnesium carbonate (80 mg)ResultsThe in vitro behaviour of the six antacid drugs in the presence of increasing amounts of 0.1 N HCl is represented in figure 1.Abstract DI-071 Figure 1ConclusionThe proposed method allowed us to quantitatively compare the studied antacids.According to the results, drug C slightly neutralised stomach acid without an extended effect. It can be prescribed for low and temporary gastric acidity.Drugs A, B and F had an average and extended neutralising action (pH stabilisation around 5). They can be prescribed for moderate and prolonged gastric acidity.Regarding drugs D and E which had a strong neutralising and long acting action that stabilised the pH around 7.5, they can be prescribed for high and prolonged gastric acidity.No conflict of interest.