Elucidation of the structure of drug degradation products by on‐line coupled reversed phase HPLC‐GC‐MS and on‐line derivatization

Abstract

AbstractDegradation products obtained under severe alkaline stress of the drug substance ENA 713, a compound developed for the treatment of DAT (dementia of the Alzheimer type), have been identified by on‐line coupled reversed phase HPLC‐GC‐MS as 3‐hydroxyaceto‐phenone and 3‐hydroxystyrene. Their structures were proven by mass spectroscopic investigation of the products obtained by on‐column derivatization during LC‐GC transfer. On‐column trimethyl‐silylation and bromination of the degradation products during the transfer were achieved by the introduction of the reagent via the loop‐type interface. The usefulness of the technique was further demonstrated by the on‐column methylation of carboxylic acids with diazomethane solution (using naproxen as model compound). First results are also given of the use of the liquid‐liquid extraction unit of the LC‐GC interface for extractive derivatization during reversed phase HPLC‐GC‐MS transfer.