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Glutathione (GSH) is the major endogenous antioxidant produced by the cells. In ADMET studies (Absorption, Distribution, Metabolism Elimination and Toxicology), the potential toxicity of a drug candidate can be evaluated by testing the reactive intermediate formation with GSH. A representative reaction involves in vitro incubation of a drug candidate with an excess of GSH in hepatic microsomes or hepatocytes. AFFINIMIP® SPE GSH enables the separation between excess of GSH, GSH adduct(s) and the drug candidate. A sample issued from incubation mixture containing an excess of GSH, drug candidate and traces of GSH adduct(s) is loaded on AFFINIMIP® SPE GSH. The drug candidates are eliminated during the loading and the washing steps while GSH-adduct(s) are extracted in the elution step. This collection fraction can be subject to classical analytical methods to detect GSH-adducts with a better sensitivity. AFFINIMIP® SPE GSH enables a specific retention of free GSH which is completely removed. Microsome incubation of GSH with drug candidates Acetaminophen and Clozapine was purified with AFFINIMIP® GSH. The drug candidates are eliminated during the loading and the washing steps while GSH adduct(s) are extracted in the elution step with a high recovery (>80%). In addition, AFFINIMIP® GSH permits a specific retention of free GSH which is completely removed. Application note - AFFINIMIP® SPE GSHUnique separation system for qualitative analysis of GSH- adducts (ADMET studies)
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