Enantioselective Separation of Antiretroviral Drug Combinations on Immobilized Polysaccharide CSPs Under Subcritical Conditions Using Supercritical Fluid Chromatography Apparatus

Abstract

A stereoselective method has been developed for the chiral separation of the enantiomers of eight antiretroviral (ARV) drugs under subcritical conditions using a supercritical fluid chromatography apparatus. The ARVs: abacavir, tenofovir alafenamide, lamivudine, efavirenz, atazanavir, emtricitabine, dolutegravir and darunavir, are used to treat the human immunodeficiency virus (HIV). The antiretroviral therapy has been planned to manage and control the severity of HIV and prolong the patient’s life. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy, which slows down the development of AIDS and prevents opportunistic infections that often lead to death. The immobilized meta-substituted polysaccharide-derived carbamate columns (CSPs) have been chosen for chiral SFC separation of selected ARVs. The ARVs enantioseparation was achieved on CSPs by using different alcohol co-solvents (methanol, ethanol and isopropyl alcohol) with diethylamine (DEA) as an additive to the mobile phase. These CSPs exhibit an exceptional level of complementary chiral recognition characteristics by applying different screening and method optimization strategies. The cellulose tris(3,5-dichlorophenylcarbamate) immobilized on silica gel was found to be useful for the chiral SFC analysis of abacavir, lamivudine, efavirenz combination ARV analysis, and the method was optimized by studying the effects of different mobile phase additives, column temperatures and flow rates. The amylose tris(3-chloro, 5-methylphenyl carbamate) immobilized on silica gel was found to be useful for the chiral SFC analysis of emtricitabine, abacavir and dolutegravir combination ARV drugs.