History of the prototype elaboration
After two years of investigations, based on the collaboration between several departments of the College of Engineering and Architecture of Fribourg (EIA-FR), a first capillary electrophoresis (CE) prototype was built during the 2006-2007 period, during which the mechanical and electronic issues were assessed, including an original detection device built in HES Fribourg on the basis of diode technology.
The second prototype, achieved during the 2007-2008 period, corrected numerous technical issues and particular attention was paid to the robustness of the system in order to anticipate the problems that can be encountered in emerging countries.
For this purpose, a diploma work carried out by a student of the Tecnologico de Monterrey Mexico was supervised by Professors Claude Rohrbasser (EIA-FR) and Serge Rudaz (LCAP-UNIGE) in Switzerland from May to October 2009. The student, who had no prior knowledge regarding CE, was able to elaborate methods for drug analysis with this low-cost CE.
Six active principles, representing eight different chemicals in various therapeutic fields were selected. This selection covers different important health problems of major developing countries. From an analytical and technical point of view, this selection represented various physico-chemical structures, including acidic and basic compounds.
After qualitative and quantitative assays as well as thorough technical evaluation carried out by recognized specialists in the field of pharmaceutical sciences (Laboratory of Pharmaceutical Analysis of the University of Geneva), several modifications were proposed to improve the technical requirements of a final prototype.
A complete revision was achieved within the same concept, namely a low-cost and user friendly analytical device, including a new electronic of the detection system based on LEDs (Light-Emitting Diodes). The latter, less expensive to produce than a usual UV-Vis diode array detector, enabled very low analyte concentrations (ppm level, i.e. 1 mg/L) to be detected.
The data acquisition and processing software was also developed at EIA-FR by extending a software (Chromatos) initially created for gas chromatography (GC) and liquid chromatography (LC).
Drug analysis by capillary electrophoresis
CE is already used for different purposes in pharmaceutical analysis and several methods have been developed for the assay of compounds (main components, by-products, impurities) in drug substances and formulations as well as for the quantification of drugs and metabolites in various matrices. CE is now recognized by numerous Pharmacopeias and can therefore be used as a validated analytical procedure according to international guideline recommendations.
In order to validate the concept, Prof. P. Bonnabry, chief pharmacist of the University Hospitals of Geneva, selected eight initial representative active compounds (amoxicillin, cotrimoxazole, furosemide, lamivudine/zidovudine/nevirapine, quinidine, rifampicin) for their various physico-chemical properties (acidic, basic or neutral analytes, pKa, log P, etc.). Their drug formulations were analyzed with the developed CE system. The results were convincing and comparable to analyses performed with a commercial CE system.
The next step was to extend the number of drugs for which a method is available.
A systematic approach is currently carried out, involving the overall evaluation of active principles mentioned in the WHO list of essential medicines1. This list is suited to the needs of developing countries and is the reference for organizing and rationalizing the drug supply in low-income countries. The final objective is to provide a few methods for as many as possible of the drugs included in this list, with exceptions for drugs that are almost not used and those for which the analytical CE method is not appropriate. To be pertinent in the sequence of method development, we have launched several collaborations with NGOs (e.g. Pharmaciens sans Frontières) involved in providing drugs in developing countries.