ELUCIDATION OF THE STRUCTURE OF DRUG DEGRADATION PRODUCTS BY ONLINE COUPLED REVERSED-PHASE HPLC-GC-MS AND ONLINE DERIVATIZATION

Degradation products obtained under severe alkaline stress of the drug substance ENA 713, a compound developed for the treatment of DAT (dem entia of the Alzheimer type), have been identified by on-line coupled reversed phase HPLC-GC-MS as 3-hydroxyacetophenone and 3-hydroxystyren e. Their structures were proven by mass spectroscopic investigation of the products obtained by on-column derivatization during LC-GC transf er. On-column trimethylsilylation and bromination of the degradation p roducts during the transfer were achieved by the introduction of the r eagent via the loop-type interface. The usefulness of the technique wa s further demonstrated by the on-column methylation of carboxylic acid s with diazomethane solution (using naproxen as model compound). First results are also given of the use of the liquid-liquid extraction uni t of the LC-GC interface for extractive derivatization during reversed phase HPLC-GC-MS transfer.