LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETRY DETERMINATION METHOD OF BENCYCLOQUIDIUM BROMIDE: APPLICATION TO DRUG INTERACTION STUDY IN HUMAN

Objective: This study was conducted to develop a sensitive and effective LC-MS/MS method for the determination of bencycloquidium bromide (BCQB) and its application in pharmacokinetic drug interaction study between BCQB and paroxetine. Methods: The chromatographic separation was performed on Hedera ODS-2 C18 column with a mobile phase consisted of acetonitrile-10 mmol/l ammonium acetate containing 0.2% acetic acid (33:67, v/v) at 550 μl/min, and the plasma samples were processed using solid-phase extraction. The MS/MS transitions were m/z 330.2 → 142.0 for BCQB and m/z 344.2 → 156.1 for the I. S in positive ESI mode. Results: The validated method was linear over the concentration range of 2-1200 pg/ml with the correlation coefficient r2>0.998. The intra-and inter-batch precisions of the assay were lower than 8.2% and 9.1%, respectively. The lower limit of quantification (LLOQ) was 2 pg/ml. The stability data at different storage conditions of BCQB were within±5% RE. The mean AUC0-36 of BCQB was increased by approximately 33%, after the administration of BCQB alone and upon co-administration with paroxetine during the drug interaction study. Conclusion: The LC-MS/MS method validated in this study was robust, reproducible, accurate, precise and reliable and was successfully applied in the pharmacokinetic drug interaction studies

IDENTIFICATION AND QUANTIFICATION OF PHOSPHODIESTERASE-5 INHIBITOR AS FALSIFIED IN ‘‘NATURAL’’ MALAYSIAN HERBAL APHRODISIACS SOLD IN SOME BENINESE MARKETS

Objective: Nowadays, there have been several reports of herbal products falsified with well-known synthetic molecules, leading to harmful health consequences for the consumer. The aim of this study was to assess the profile of ‘natural' herbal aphrodisiacs in the local markets of the municipalities of Cotonou and Abomey-Calavi in Benin and to screen some of them for the presence of additives such as sildenafil and tadalafil. Methods: A non-probability survey was conducted to identify the available aphrodisiacs and their characteristics. Some of them were then selected for analysis. Thin Layer Chromatography (TLC) was adopted for qualitative detection. The TLC positive extracts were then analyzed by HPLC on a C18 column with a mobile phase consisting of a mixture of 0.05M phosphate buffer (pH 5.8), acetonitrile and methanol (30:50:20). The Detection was performed at 290 nm. Results: Seventy-seven aphrodisiacs were identified and from these, 18 were selected for analysis. Six of them were adulterated with tadalafil. The concentration of tadalafil in the samples was 1.7 to 4.6 times higher than the recommended dose of 20 mg. Conclusion: This work opens the door to the need to control ‘‘natural’’ labeled products in order to ensure their quality

APPLICATION OF DESIGN SPACE OPTIMIZATION STRATEGY TO THE DEVELOPMENT OF LC METHODS FOR SIMULTANEOUS ANALYSIS OF 18 ANTIRETROVIRAL MEDICINES AND 4 MAJOR EXCIPIENTS USED IN VARIOUS PHARMACEUTICAL FORMULATIONS

peer reviewedtAs one of the world’s most significant public health challenges in low- and middle-income countries,HIV/AIDS deserves to be treated with appropriate medicines, however which are not spared from coun-terfeiting. For that, we developed screening and specific HPLC methods that can analyze 18 antiretroviralmedicines (ARV) and 4 major excipients. Design of experiments and design space methodology wereinitially applied for 15 ARV and the 4 excipients with prediction thanks to Monte Carlo simulations andfocusing on rapidity and affordability thus using short column and low cost organic solvent (methanol)in gradient mode with 10 mM buffer solutions of ammonium hydrogen carbonate. Two other specificmethods dedicated to ARV in liquid and in solid dosage formulations were also predicted and opti-mized. We checked the ability of one method for the analysis of a fixed-dose combination composedby emtricitabine/tenofovir/efavirenz in tablet formulations. Satisfying validation results were obtainedby applying the total error approach taking into account the accuracy profile as decision tool. Then, thevalidated method was applied to test two samples coded A and B, and claimed to contain the tested ARV.Assay results were satisfying only for sample B

Simple LC Isocratic Methods Development, Validation, and Application in the Analysis of Poor Quality Antimalarial Medicines

peer reviewedLiquid chromatographic methods in isocratic mode for the analysis of poor quality medicines are privileged due to their simplicity and facility in methods development. They are generally fast; do not need to be re-equilibrated between sample injections; have larger flexibility with acceptable changes on different column dimensions; and are applicable to LC systems equipped with simple or high developed pumps. In this study, we focused on developing simple isocratic methods using classical mobile phase composed by methanol and ammonium formate buffer for the analysis of most common antimalarial medicines marketed in malaria endemic countries and susceptible of being counterfeit/falsified, substandard and degraded. The selected medicines were quinine and related cinchona alkaloids in tablets and injectable forms; artemether/ lumefantrine tablets; and artemisinin compounds (arteether, artemether, and artesunate) in injectable forms. The current methods were developed thanks to simple methodological approach consisting in sequential isocratic runs through adjustment or adaptation of existing methods to obtain optimal analytical conditions without complex design of experiments that might be long and costly. Then, the new methods presented shorter analysis time; allowed increase of sample analysis throughput; and obviously consumed little mobile phase solvents on classical analytical columns: 50 - 250 mm of length (L), 4.6 mm of internal diameter (I.D.), and 3.5 - 5.0 μm of particle size (dp)

Identification et étude phytochimique de plantes utilisées dans le traitement traditionnel de l’ulcère de Buruli au Bénin

Le traitement traditionnel de l’ulcère de Buruli (UB) au Bénin se fait principalement à base de plantes. L’enquête ethnobotanique menée auprès de 17 tradipraticiens dans la commune de Ouinhi (département du Zou) a répertorié 49 plantes différentes utilisées pour traiter cette maladie. Deux de ces plantes présentent un fort taux d’utilisation : Erythrophleum suaveolens (Guill. et Perr.) Brenan et Strophanthus hispidus DC. L’étude phytochimique de dix-sept de ces plantes révèle la présence de grands groupes chimiques dont de nombreux composés possèdent diverses propriétés notamment anti-oedémateuses, anti-inflammatoires, antibactériennes, antiseptiques, sédatives, analgésiques, anesthésiques, cicatrisantes qui pourraient intervenir dans le traitement de l’UB. Des recherches complémentaires sont nécessaires pour identifier, isoler et purifier les composés de ces groupes chimiques présents dans les plantes et étudier leur place relative dans le traitement de l’UB

Quality assessment of three imidazole antiparasitics (albendazole, mebendazole and metronidazole) sold in Benin

peer reviewedIllicit circuit of medicines disrupts the quality assurance system and the rational use of medicines. Substandard and falsified (SF) medicines present a major risk for the public health, due to lack of active ingredient and/or toxicity of certain components. The purpose of this study was to evaluate the quality of three imidazole antiparasitic medicines (albendazole, mebendazole and metronidazole tablets) sold in Benin, to describe the different forms of non-compliances of the medicines sold in the illicit circuit. The samples were collected in the formal and illicit (informal) circuits. The results appeared as follows: irregularities of packaging (25.5% of samples from the illicit circuit); mass uniformity test (14.7% of samples from the illicit circuit were noncompliant); disintegration test (2.1% of samples from the illicit circuit and 3.5% from the formal circuit were non-compliant); identification (all samples were compliant) and assay (47.1% of samples from the informal circuit were non-compliant among which 26.5% of under-dosing and 20.6% of overdose). In sum, there were respectively 38.3% (i.e. 18/47) and 3.5% (i.e. 2/58) of non–compliance in the illicit and formal circuit

Falsification of drugs in peri-urban areas: a sad reality

peer reviewedFalsifying drugs constitutes a scourge, a danger and a threat to public health. If the situation is already alarming at the global level, what could be expected regarding the peri-urban areas of developing countries? In order to better understand the situation in these areas and to improve the consciousness and involvement of the people living in those areas, a study was carried out to evaluate the current status of the pharmaceutical health situation of some cities in Central East and West Africa. The results illustrate the complexity to set up an adequate pharmaceutical system in these areas that seem to escape to the control of the official health authorities. On the other hand, the analytical results carried out by means of generic analytical methods on antibiotic, antimalarial and non-steroidal anti-inflammatory drugs sampled in the peri-urban areas, are revelatory and confirm the sad reality of false drugs in those areas

C19- Evaluation du profil d’acide gras et statuts d’oxydation de sept huiles alimentaires commercialisées au Bénin

Introduction : Les populations béninoises consomment au quotidien des huiles végétales de différent profil d’acides gras (AG) insaturés comme saturés, leur conférant des vitesses d’oxydabilité différentes. Les produits d’oxydation primaire (radicaux peroxydes) et secondaire (aldéhydes) sont nuisibles à la santé humaine et justifient la nécessité d’une évaluation de ces huiles alimentaires. Méthodologie : Cette étude préliminaire porte sur 7 marques d’huile dont 1 de tournesol, 2 de coton et 2 d’origine végétale non précisée, toutes raffinées, ainsi que 1 d'arachide et 1 de palme rouge de production artisanale locale. Le profil d’AG a été réalisé, après méthylation des AG, au moyen d’un GC-FID Trace 1310 (Thermo, Italy), équipé d’un Triplus autosampler (Thermo, Italy). La séparation a été réalisée sur une colonne capillaire RT2560 (100m x 0,25mm, df : 0,25µm) avec une injection de 1 µL on-column à 225°C. Le temps d’analyse est de 83 min avec un gradient de température du four allant de 80-235°C. Le H2 est utilisé comme gaz vecteur à 1,2 ml/min. L’oxydation primaire et secondaire ont été déterminées par l’indice de peroxyde (IP) et l’indice de p-anisidine (Ip-A) selon la méthode AOCS. Résultats et Discussion : L’analyse des résultats rapporte les données suivantes : L’huile de tournesol contient 60% d’acide linoléique (AL), 29% d’acide oléique (AO) ; le coton 54% d’AL, 17% d’AO et 24% d’acide palmitique (AP) contre 33%, 43% et 13% respectivement pour l’huile d'arachide. Le profil d’AG des 02 huiles raffinées et de l’huile de palme rouge est similaire avec 40- 41% d’AP et 41-46% d’AO. Les 02 marques d’huile de coton et 01 de tournesol présentent une forte oxydation primaire avec des valeurs de IP de 16; 25 et 28,9 méq O2 actif/kg (norme < 15). Les huiles d’arachide (IP=3), de palme (IP=6,6) et les 2 huiles végétales raffinées (IP= 10,35 et 12,38) sont conformes. Quant à l’oxydation secondaire, toutes les huiles analysée sont conformes, 0≤.Ip-A≤ 6,21 (norme < 10) après 6 semaines de conservation dans les conditions classiques (fermeture non scellée). Conclusion : Cette étude préliminaire révèle que les huiles de coton et de tournesol subissent une oxydation rapide comparée aux huiles d’arachide et de palme. Des huiles de palme blanchies sans étiquetage adéquate sont commercialisées et tromperaient la vigilance des populations