DETECTION OF ORTHO-DIAMINE RESIDUES IN ANALYTES CONTAINING RESIDUAL CYCLIZING AGENTS BACKGROUND OF THE INVENTION

摘要

The present invention relates to a novel method for the analytical determination of an aromatic ortho diamine contaminant in a pharmaceutical compound or intermediate thereof prepared by treating said aromatic ortho diamine with a cyclizing agent. The method comprises the steps of: (i) treating the pharmaceutical compound or intermediate thereof containing the contaminant with acetone to form a 2,2,4-trimethyl-1 ,5-benzodiazepine derivative of the aromatic ortho diamine contaminant, (ii) determining the quantity of the 2,2,4-trimethyl-1 ,5-benzodiazepine derivative in the pharmaceutical compound or intermediate thereof, preferably by HPLC and (iii) correlating the quantity of the 2,2,4- trimethyl-1,5-benzodiazepine derivative with the quantity of aromatic ortho diamine contaminant originally present in the pharmaceutical compound or intermediate thereof. Formation of the 2,2,4-trimethyl-1 ,5-benzodiazepine derivative occurs rapidly under mild conditions thereby eliminating interference by residual cyclizing agent and enabling detection of aromatic ortho diamines at ppm levels.