Capillary electrophoresis (CE) for the quality control of drugs and counterfeit medicines
The proportion of counterfeit medicines has dramatically increased in the last few years. According to numerous official sources, for some pharmaceutical wholesalers in African countries, the proportion has reached 80%. The fight against this calamity is complex and different levels of action are necessary. The safety of the supply chain must be improved (e.g. by carefully selecting the providers), the design of the drugs can contain anticounterfeiting techniques (e.g. serialization, hologram), and quality control of batches imported into the different countries can be implemented. Unfortunately, this latter strategy is often difficult to apply due to a lack of suitable analytical equipment in developing countries.
The College of Engineering and Architecture of Fribourg (EIA-FR), member of the University of Applied Sciences (Western Switzerland), has therefore decided to collaborate with the School of Pharmaceutical Sciences, University of Geneva / University of Lausanne (Switzerland), in order to build a low-cost analytical device, namely capillary electrophoresis (CE), with the aim of using it for educational purposes and helping developing and transitional countries to fight against counterfeit medicines.
The new CE device is dedicated to conventional quality control of drug material (active principal ingredient, API) and drug products (pharmaceutical formulations). CE should be successful in routine analyses due to its short analysis time and method development, simple instrumentation, low sample and solvent consumption as well as to reduced operating costs. Therefore, CE is perfectly adapted to rapidly evaluate the quality of drugs, to establish the presence and the concentration of the active principles and to give evidence regarding the amount of degradation impurities.
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.