TY - JOUR
T1 - Simultaneous quantification of zidovudine, stavudine, lamivudine and nevirapine by Micellar Electrokinetic Capillary Chromatography
AU - Gras, Alain
AU - Yegles, Michel
AU - Karasi, Jean Claude
AU - Schmit, Jean Claude
AU - Seguin-Devaux, Carole
AU - Schneider, Serge
PY - 2013
Y1 - 2013
N2 - Purpose: Recent improvements to the availability of antiretroviral therapy in Sub-Saharan Africa can be attributed to the generic formulation of antiretroviral drugs. Quality drug surveillance, routine supervision and adherence data are however restricted owing to a fundamental lack of resources in the area. Accordingly we have developed an affordable micellar electrokinetic capillary chromatography (MEKC) method for the simultaneous detection and quantification of zidovudine, stavudine, lamivudine and nevirapine in plasma. Methods: The antiretroviral drugs were extracted by solid phase extraction. Various factors influencing separation of the four drugs have been optimized. A buffer consisting of 5 mM sodium tetraborate at pH 9.8, containing 50 mM SDS, 30% methanol and 5% ethanol was found to be particularly suitable and the MEKC method was validated. Results: All validation parameters were within the 20% acceptation limit, except for the interday precision of stavudine which required a daily calibration curve. The limit of quantification (LOQ) for zidovudine, stavudine, lamivudine and nevirapine were 0.037, 0.051, 0.029 and 0.028 mg/L respectively and were below the therapeutic concentration ranges of each drug. The optimized MEKC method was successfully applied to 16 human plasma samples. Conclusion: Our sensitive and validated method was demonstrated to be suitable for simultaneous detection and quantification of zidovudine, stavudine, lamivudine and nevirapine. This cost-effective method could be of interest for resource limited countries not only for adherence or therapeutic monitoring but also for steady-state pharmacokinetic studies of generic ARV drugs.
AB - Purpose: Recent improvements to the availability of antiretroviral therapy in Sub-Saharan Africa can be attributed to the generic formulation of antiretroviral drugs. Quality drug surveillance, routine supervision and adherence data are however restricted owing to a fundamental lack of resources in the area. Accordingly we have developed an affordable micellar electrokinetic capillary chromatography (MEKC) method for the simultaneous detection and quantification of zidovudine, stavudine, lamivudine and nevirapine in plasma. Methods: The antiretroviral drugs were extracted by solid phase extraction. Various factors influencing separation of the four drugs have been optimized. A buffer consisting of 5 mM sodium tetraborate at pH 9.8, containing 50 mM SDS, 30% methanol and 5% ethanol was found to be particularly suitable and the MEKC method was validated. Results: All validation parameters were within the 20% acceptation limit, except for the interday precision of stavudine which required a daily calibration curve. The limit of quantification (LOQ) for zidovudine, stavudine, lamivudine and nevirapine were 0.037, 0.051, 0.029 and 0.028 mg/L respectively and were below the therapeutic concentration ranges of each drug. The optimized MEKC method was successfully applied to 16 human plasma samples. Conclusion: Our sensitive and validated method was demonstrated to be suitable for simultaneous detection and quantification of zidovudine, stavudine, lamivudine and nevirapine. This cost-effective method could be of interest for resource limited countries not only for adherence or therapeutic monitoring but also for steady-state pharmacokinetic studies of generic ARV drugs.
KW - Capillary electrophoresis
KW - Drug monitoring
KW - Highly active antiretroviral therapy
KW - Micellar Electrokinetic Capillary Chromatography
KW - Plasma
UR - http://www.scopus.com/inward/record.url?scp=84875025437&partnerID=8YFLogxK
U2 - 10.1051/ata/2012024
DO - 10.1051/ata/2012024
M3 - Article
AN - SCOPUS:84875025437
SN - 0768-598X
VL - 24
SP - 177
EP - 183
JO - Annales de Toxicologie Analytique
JF - Annales de Toxicologie Analytique
IS - 4
ER -