Development of alternative methods for the quality control of antiretroviral drugs by capillary electrophoresis

Author(s)

Luiz Antonio Zanolli Filho

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2007-06-29

Examining board members

Marina Franco Maggi Tavares; María Segunda Aurora Prado; Maria Olimpia de Oliveira Rezende

• Advisor: Marina Franco Maggi Tavares

Abstract

There are approximately 38.6 million people infected by the immunodeficiency acquired virus (AIDS) over the world. The only way of treatment for this illness is administrating drugs that act in different points of the replicative cycle of the virus. In Brazil this illness is dealt as public calamity, being its treatment made through the national program DST/AIDS, which distributes free of charge necessary medicines for the treatment. Considering that many of these drugs are formulated by the local industries, this thesis has as objective the development of analytical methods to be applied in the pharmaceutical routine for the qualification of raw materials, as well as the quality control of the finished products. The analysis of drug formulations of nevirapine and lamivudine were carried by CZE, in acid electrolytes with pH < 2.5. For lamivudine the analysis was carried using an electrolyte composed of 0.5 % of TEA, 20 mmol.L-1 of TRIS, pH = 2.5, adjusted with phosphoric acid, with an analysis time less than 4 minutes. The method developed for the nevirapine, was lead in an electrolyte composed of 10 mmol.L-1 of phosphate buffer (pH = 2.5), with a time of analysis of 3 minutes. Another method was developed for efavirenz, estavudine and ritonavir by MEKC, using 23 a factorial design with central point, with an analysis time less then 9 minutes in an electrolyte of 20 mmol.L-1 of sodium tetraborate, 20 mmol.L-1 sodium dodecyl sulfate and 30 % acetonitrile. The developed methods were validated in accordance with official protocols, showing that these methods can be advantageously used in the analysis of pharmaceutical formulations. Another approach was to use the coupling of capillary electrophoresis with mass spectrometry, where fortified samples of urine had been analyzed. The analysis were performed using 400 mmol.L-1 formic acid and liquid sheath consisting of 0.5 % of formic acid diluted with a solution of (1:1) methanol:water, allowing the unequivocal identification detection of the drugs in the samples. (AU)