title: Application of an innovative design space optimization strategy to the development of liquid chromatographic methods to combat potentially counterfeit nonsteroidal anti-inflammatory drugs.
abstract: In the context of the battle against counterfeit medicines, an innovative methodology has been used to develop rapid and specific high performance liquid chromatographic methods to detect and determine 18 non-steroidal anti-inflammatory drugs, 5 pharmaceutical conservatives, paracetamol, chlorzoxazone, caffeine and salicylic acid. These molecules are commonly encountered alone or in combination on the market. Regrettably, a significant proportion of these consumed medicines are counterfeit or substandard, with a strong negative impact in countries of Central Africa. In this context, an innovative design space optimization strategy was successfully applied to the development of LC screening methods allowing the detection of substandard or counterfeit medicines. Using the results of a unique experimental design, the design spaces of 5 potentially relevant HPLC methods have been developed, and transferred to an ultra high performance liquid chromatographic system to evaluate the robustness of the predicted DS while providing rapid methods of analysis. Moreover, one of the methods has been fully validated using the accuracy profile as decision tool, and was then used for the quantitative determination of three active ingredients and one impurity in a common and widely used pharmaceutical formulation. The method was applied to 5 pharmaceuticals sold in the Democratic Republic of Congo. None of these pharmaceuticals was found compliant to the European Medicines Agency specifications.
authors.affiliation: Laboratory of Analytical Chemistry, CIRM, Department of Pharmacy, University of Liège, 1 Avenue de l'Hôpital, B36, B-4000 Liège, Belgium.
authors.forename: J K
authors.initials: JK
authors.lastname: Mbinze
authors.forename: P
authors.initials: P
authors.lastname: Lebrun
authors.forename: B
authors.initials: B
authors.lastname: Debrus
authors.forename: A
authors.initials: A
authors.lastname: Dispas
authors.forename: N
authors.initials: N
authors.lastname: Kalenda
authors.forename: J
authors.initials: J
authors.lastname: Mavar Tayey Mbay
authors.forename: T
authors.initials: T
authors.lastname: Schofield
authors.forename: B
authors.initials: B
authors.lastname: Boulanger
authors.forename: E
authors.initials: E
authors.lastname: Rozet
authors.forename: Ph
authors.initials: P
authors.lastname: Hubert
authors.forename: R D
authors.initials: RD
authors.lastname: Marini
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation* / Q000379:methods; D058110:Counterfeit Drugs / Q000737:chemistry*; D015195:Drug Design; D004867:Equipment Design
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D058110:Counterfeit Drugs