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)

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

Comparative study of the in-vitro dissolution profiles of generic and originator quinine sulfate by using High Performance Liquid Chromatography

peer reviewedIntroduction : La quinine est une molécule préconisée pour le traitement du paludisme dans les régions où les souches de P. falciparum sont polyrésistantes. Face à l’importante utilisation de ses médicaments génériques d’une part, et au fléau des médicaments de qualité inférieure d’autre part, il devient plus que nécessaire d’appuyer les données des tests physico-chimiques par celles de dissolution in vitro dont l’évaluation et la comparaison des cinétiques permettra de prédire le comportement in vivo du principe actif et par conséquent l’efficacité du médicament générique. L’objectif de la présente étude est de réaliser une étude comparative de la cinétique de dissolution d’un princeps et d’un générique à base de quinine comprimé 300 mg commercialisés à Kinshasa. Matériels et méthodes : L’étude a été réalisée en utilisant trois milieux de pH différents (1,2 - 4,5 - 6,8) tels que recommandés par l’Agence Européenne de Médicament et en se servant d’un appareil de dissolution, tandis que l’équipement de chromatographie liquide à haute performance couplée à un détecteur à barrette de diodes a été utilisé pour la quantification. La méthode statistique fit factor a été appliquée pour comparer les résultats de dosage de la quinine dans les trois milieux tout en ayant évalué le biais à différents temps de dissolution. Résultats : Les différents échantillons de médicaments générique et princeps ont été conformes quant à l’identification et au dosage de la quinine, par contre leurs cinétiques de dissolution étaient non similaires. Discussion : Ceci pourrait avoir une influence sur l’efficacité du produit générique et la sécurité des consommateurs, dénotant l’importance d’examiner les profils de dissolution des génériques avant toute autorisation de mise sur le marché plus particulièrement dans les pays en voie de développement

C42 - Optimisation d’une formule de comprime matriciel à base de spiruline enrichi en vitamine C

La spiruline est une algue fortement consommée dans le monde comme complément alimentaire en raison de son grand potentiel nutritionnel. Elle se trouve toutefois exempte de vitamine C, une vitamine capitale pour le bon fonctionnement de l’organisme humain compte tenu notamment de son pouvoir immunostimulant. L’objectif de notre travail était de formuler des comprimés matriciels de spiruline et de la vitamine C, qui assureront une libération prolongée et une meilleure absorption de la vitamine C ; cette dernière étant sujette à un mécanisme de saturation lors de son absorption. Nous sommes donc partis d’une formule galénique uniquement à base de vitamine C (A1), pour ensuite réduire la proportion de vitamine C au profit de la poudre de spiruline (S). Les comprimés fabriqués ont subi les différents tests pharmaco-techniques pour le contrôle de leur qualité. Les résultats de ce contrôle ont montré une bonne distribution des mélanges de poudres dans nos comprimés à l’issue du test d’uniformité de masse (A1 : 405±8,8 mg ; S : 665±9,4 mg), des résultats également satisfaisants pour les tests d’uniformité de teneur (A1 :175 ± 15,7 mg S : 41 ± 3,4 mg), de désagrégation (300 minutes) et de dissolution avec 45 % de la vitamine C dissoute au bout de 4 h de test (Comprimé S) contre 85% pour A1. Seul le test de friabilité était non satisfaisant témoignant la nécessité d’améliorer les propriétés physiques de nos poudres avant la compression. Ce travail sera approfondi en vue de l’installation sur place d’une unité de production desdits comprimés pour leur mise sur le marché.