Depuis la loi no 17-04 du code national du médicament et de pharmacie, paru au journal officiel du 22 novembre 2006, les radiotraceurs utilisés en médecine nucléaire au Maroc sont devenus des ...médicaments diagnostiques ou thérapeutiques. À ce titre, les médicaments radiopharmaceutiques doivent satisfaire aux exigences de qualité pharmaceutique qui s’appliquent à tout médicament (Payoux et Prigent, 2009 5). Cette tâche, qui ne concerne qu’une des obligations légales concernant la radiopharmacie, doit être réalisée sous la responsabilité d’un radiopharmacien ou à défaut d’un pharmacien ayant acquis des compétences pratiques en radioéléments à visée diagnostique ou thérapeutique (Morera et al., 1993 6). Dans la situation des établissements hospitaliers qui tardent à appliquer cette loi, comme dans le cas du Maroc, le service pharmaceutique ne peut se désintéresser de la question. Dans le cadre de ce travail, nous nous sommes proposés de présenter la démarche qualité au sein du service de médecine nucléaire de l’hôpital Ibn Sina du centre hospitalier universitaire Ibn Sina. Cette démarche a débuté il y a deux ans et vise à améliorer le bon usage des radiopharmaceutiques, contribuer à la qualité des actes diagnostiques et thérapeutiques et surtout assurer les conditions optimales de sécurité pour le personnel et le patient. Cette activité pharmaceutique touche de près l’approvisionnement, la préparation, la dispensation et la gestion des déchets radioactifs résultant de la manipulation des médicaments radiopharmaceutiques au service. Le contrôle de qualité des préparations reconstituées a été également intégré dans le programme assurance qualité, malgré les contraintes techniques rencontrées au cours de leur réalisation. Notre documentation de base se référait à la pharmacopée européenne (Pharmacopée européenne, 2010 8), au référentiel de radiopharmacie (Bonnot-Lours, 2000 2) et aux bonnes pratiques de préparation (Afssaps, 2006 3). La réflexion était pluridisciplinaire ayant impliqué un médecin nucléaire, les physiciens, une pharmacienne de la pharmacie de l’hôpital, des chimistes de la direction des contrôles de médicaments, les informaticiens de l’hôpital et le personnel paramédical (techniciens, infirmiers et agents d’entretien) du service.
Since Law no 17-04 of the national code of medicine and pharmacy, published in the official newspaper of November 22, 2006, radiotracers used in nuclear medicine in Morocco have become drugs or diagnostic radiopharmaceuticals. As such, radiopharamaceuticals must meet the requirements of pharmaceutical quality and control that apply to any drug (Payoux and Prigent, 2009 5). This task must be undertaken under the pharmacist's responsibility with a specific skill known as “radiopharmacist” (Morera et al., 1993 6). In the situation of Moroccan hospital, like Ibn Sina hospital for which the only law of the national code is partially applied, nevertheless the pharmacy department cannot ignore this issue. As part of this work, we present the proposed new quality installation service for 24 months. It aims to improve the proper use of radiopharmaceuticals, to contribute to the quality of diagnostic and therapeutic procedures and especially to ensure the optimal conditions of safety for staff and patients. This activity closely affects the pharmaceutical supply, preparation, dispensing and management of radioactive waste resulting from handling radiopharmaceutical drugs. Radiopharmaceutical quality control of was also integrated into the global quality control program, despite the technical constraints encountered during their day-to-day practice. Our basic documentation referred to European directives (Pharmacopée européenne, 2010 8), French Pharmacopoeia (Bonnot-Lours, 2000 2) and good preparation practise rules (Afssaps, 2006 3). The reflection was undertaken within a multidisciplinary framework: nuclear physician, physicists, a pharmacist working in hospitalpharmacy, chemists of the drug control department, computer and paramedical staff (technicians, nurses, and cleaners).
This paper presents a new procedure to optimize the geometric parameters of a n-type coaxial HPGe detector. It is based on a statistical technique called “Design of Experiments” (DoE). This technique ...aims to identify the most influential parameters and to determine the optimal configuration. In this work, The effects of each parameter on the detector responses have been investigated by a fractional factorial design. Only the most influential factors contributing to the detector response have been selected. Precise modeling of these factors was then performed using a full factorial design. Based on the results obtained from this design, the full energy peak efficiencies according to the geometric parameters were modeled by a multiple-linear regression. These models have been statistically validated by analysis of variance (ANOVA). The optimal combination of the geometric parameters has been identified using the desirability function approach, which is a useful tool to optimize multi-response problems. A verification test was performed to validate the results obtained. It was observed that the relative deviation found between experimental and simulated values was less than 5%.
•Optimization of geometrical dimensions of an HPGe detector.•Application of Monte Carlo simulation and “Design of Experiments” technique.•Investigating influence of each detector parameter on the FEPE.•Achieving good agreement between the measured and the simulated results.
This work aims to establish some X-ray qualities recommended by the International Standard Organization (ISO) using the half-value layer (HVL) and Hp(10) dosimetry approaches. The HVL values of the ...following qualities N-60, N-80, N-100, N-150 and N-250 were determined using various attenuation layers. The obtained results were compared to those of reference X-ray beam qualities and a good agreement was found (difference less than 5% for all qualities). The GAMOS (Geant4-based Architecture for Medicine-Oriented Simulations) radiation transport Monte Carlo toolkit was employed to simulate the production of X-ray spectra. The characteristics HVLs, mean energy and the spectral resolution of simulated spectra have been calculated and turned out to be conform to the ISO reference ones (difference less than the limit allowed by ISO). Furthermore, the conversion coefficients from air kerma to personal dose equivalent for simulated and measured spectra were fairly similar (the maximum difference less than 4.2%).
The main objective of this work is to perform a neutronic study of the 2 MW TRIGA MARK-II research reactor of the National Centre of Sciences, Energy and Nuclear Techniques (CNESTEN), Rabat, Morocco ...and then validate the results by comparing the experimental values and those published for an ordinary 2 MW TRIGA MARK II research reactor. The core diffusion code DONJON5 and the lattice code DRAGON5 were coupled to perform a full model of the TRIGA core and their consistency and accuracy were established by benchmarking the TRIGA experiments. In this study, the nuclear data libraries ENDF/B-VII.1 and JEFF3.1 based on 172 energy groups were used. The group constants of all the reactor components were generated using DRAGON5 code and the collision probability method. These group constants were used then in the DONJON5 core code to calculate the multiplication factor, core excess reactivity, total and integral control rods worth as well as power peaking factors. Good agreement found between the calculated and measured results.
•Neutronic calculations of the TRIGA MARK II research reactor.•Validation of the deterministic transport code DRAGON5 and diffusion code DONJON5.•Calculation and analysis of control rod worth, excess reactivity as well as power peaking factors by deterministic codes.•The good consistency of the results ensures that a thermal-hydraulic analysis will be performed for TRIGA reacteor.•To rely on DRAGON5 and DONJON5 codes for TRIGA Mark-II calculations.
In this work, we present our MCNP6.1 modeling of some critical fast experimental benchmarks, aiming to qualify our cross section libraries derived from ENDF/B-VII.1, ENDF/B-VII, JEFF-3.1, JENDL-3.3, ...and JENDL-4.0. The analyzed benchmarks are characterized by simple geometries which helps to have taken precise results, and concerning the type: HEU-MET-FAST (highly enriched uranium). Those benchmarks are extracted from the
International Handbook of Evaluated Criticality Safety Benchmark Experiments (IHECSBE)
published by the Nuclear Energy Agency
1
. A detailed comparison of the results of our simulation was made in order to highlight the influence of these nuclear data types on our calculations, due to its importance for the stability of nuclear reactors. We interpreted the difference between calculation and experiment (
) for the principal parameter
through a comparison of the fission and capture rates of the major fissile elements. The different spectral indices F28/F25, F49/F25, F37/F25, C28/F25, and F23/F25 at the cores center are also calculated. For the majority of the studied HEU (highly enriched uranium) benchmark cases, The ENDF/B-VII and JEFF-3.1 have a good agreement with the experimental ones, concerning the
results. The average discrepancy from the experimental values for ENDF/B-VII is 0.42
, and 0.39
for JEFF-3.1. An overestimation was observed for most evaluations concerning benchmarks with tungsten carbonate reflectors. The best results were obtained by JENDL-3.3, with a maximal discrepancy
estimated 0.47
concerning fission rate, and 4.25
for capture rate. In analyzing the spectral indices, for GODIVA and FLATTOP-25, the best results were obtained by JENDL-4.0 with a maximal discrepancy of 2.66
.
An innovative simple, fast, precise and accurate ultra-high performance liquid chromatography (UPLC) method was developed for the determination of diclofenac (Dic) along with its impurities including ...the new dimer impurity in various pharmaceutical dosage forms. An Acquity HSS T3 (C18, 100×2.1mm, 1.8μm) column in gradient mode was used with mobile phase comprising of phosphoric acid, which has a pH value of 2.3 and methanol. The flow rate and the injection volume were set at 0.35ml·min(-1) and 1μl, respectively, and the UV detection was carried out at 254nm by using photodiode array detector. Dic was subjected to stress conditions from acid, base, hydrolytic, thermal, oxidative and photolytic degradation. The new developed method was successfully validated in accordance to the International Conference on Harmonization (ICH) guidelines with respect to specificity, limit of detection, limit of quantitation, precision, linearity, accuracy and robustness. The degradation products were well resolved from main peak and its seven impurities, proving the specificity power of the method. The method showed good linearity with consistent recoveries for Dic content and its impurities. The relative percentage of standard deviation obtained for the repeatability and intermediate precision experiments was less than 3% and LOQ was less than 0.5μg·ml(-1) for all compounds. The new proposed method was found to be accurate, precise, specific, linear and robust. In addition, the method was successfully applied for the assay determination of Dic and its impurities in the several pharmaceutical dosage forms.
The comparative pharmacokinetic behavior of albendazole (ABZ) and its new benzimidazol prodrug 1-tert-butyloxycarbonyl-5-propylthio-1-H-benzimidazol-2ylcarbamate of methyl (ABZBoc), following their ...oral administration (10mg/kg) to healthy dogs was explored. Blood samples were obtained serially over a 24h period after treatment, then the plasma was analyzed by high-performance liquid chromatography (HPLC) to search the albendazole metabolites (ABZSO and ABZSO2). However, the albendazole parent drug was not detectable at any time after both treatments (ABZ and ABZBoc). By albendazole metabolites (ABZSO and ABZSO2) were the analytes recovered in the plasma after oral administration of ABZ and ABZBoc. Furthermore, some amounts of ABZBoc were also available in the plasma samples treated with this new produg. The plasma profile of each analyte followed a similar pattern after both treatments, the active metabolite (ABZSO) was the major analyte recovered in plasma (between 1 and 24h post-treatment). The pharmacokinetic parameters of both groups were calculated (Cmax, Tmax, t1/2, AUC0-›∞), and analyzed using the Student's t-test, P<0.05. Thus,the pharmacokinetic analysis indicated four statistically significant changes in the pharmacokinetic parameters defined above of the albendazole metabolites (ABZSO, ABZSO2) between the group treated with albendazole (group A) and that treated with ABZBoc prodrug (group B). Hence, the levels of the various pharmacokinetics parameters were low in the group treated with prodrug, as well they did not reach equivalent concentrations to that of albendazole. These differences between albendazole and its new prodrug may be explained by the fact that ABZBoc prodrug was not effectively reduced in the intestine of dogs.
A gradient reversed phase high-performance liquid chromatography (RP-HPLC) method with ultraviolet (UV) detection to analyze hydrochlorothiazide (HCT) and valsartan (VS) simultaneously in a tablet ...formulation during forced degradation studies was developed. This method was validated using a novel approach, namely, the accuracy profile or total errors approach. The robustness of the method was evaluated using a Plackett-Burman design for eight factors. The algorithm of Dong was applied to determine the significant factor effects. The validation results showed that the method is precise (RSD: 1.14% for HCT and 0.43% for VS) and accurate (mean recovery: 99.90% for HCT and 99.98% for VS). On the other hand, the results of the robustness study showed that the type of column was the important factor which affects a number of responses, namely, the asymmetry factor (AF), retention time (RT), and resolution (RS). However, the assay results were not affected; therefore, the method can be considered robust. Finally, the method was applied to study the stability of HCT and VS under forced conditions. Significant results were obtained with basic hydrolysis, oxidation, and thermal stress, while the accelerated and acidic conditions did not affect the stability of HCT or VS.
A simple, rapid, and sensitive RP-HPLC method using photodiode array detection was developed and validated for the simultaneous determination of butylhydroxyanisol and simvastatin with its impurities ...in tablet forms. Chromatographic separation was achieved on a Phenomenex Hypersil (250×4.6 mm, 5 μm) column using the mobile phase acetonitrile-sodium acetate (12 mM) buffered to 4.2 with glacial acetic acid. The flow rate was 1.7 mL/min, and the UV detection were made at 238 nm for simvastatin and its impurities and at 290 nm for butylhydroxyanisol. The system suitability solution used for peak impurity identification was generated in-situ without use of any impurity reference standard. The method was validated according to ICH Q2(R1) guidelines, and the acceptance criteria for accuracy, precision, linearity, specificity, robustness, LOD, and LOQ, were met in all cases. Moreover, the reproducibility results obtained by 22 Official Medicines Control Laboratories (OMCL) of European Directorate were satisfactory. The compounds selected for impurity validation were based on those found during long term and accelerate stability studies carried out on several formulation tablets from Moroccan and other markets. The described method was robust and successfully applied in quality control laboratories for routine analysis to determine the butylhydroxyanisol and simvastatin with its impurities content in tablet dosage forms.
This work aims to establish some X-ray qualities recommended by the International Standard Organization (ISO) using the half-value layer (HVL) and Hp(10) dosimetry approaches. The HVL values of the ...following qualities N-60, N-80, N-100, N-150 and N-250 were determined using various attenuation layers. The obtained results were compared to those of reference X-ray beam qualities and a good agreement was found (difference less than 5% for all qualities). The GAMOS (Geant4-based Architecture for Medicine-Oriented Simulations) radiation transport Monte Carlo toolkit was employed to simulate the production of X-ray spectra. The characteristics HVLs, mean energy and the spectral resolution of simulated spectra have been calculated and turned out to be conform to the ISO reference ones (difference less than the limit allowed by ISO). Furthermore, the conversion coefficients from air kerma to personal dose equivalent for simulated and measured spectra were fairly similar (the maximum difference less than 4.2%).
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