Development of a generic flow injection analysis method for compounds witha secondary amine or amide function, using an experimental design approachI. Selection and evaluations of the FIA system parameters

A generic flow injection analysis (FIA) method to determine compounds with a secondary amine or an amide in their structure was developed. A first par t of the development, namely the selection and evaluation of the FIA system , is described. A chemical reaction with sodium hypochlorite (NaOCI) first converts the secondary amine or the amide to a primary amine. This is follo wed by reaction of the primary amine with o-phthataldehyde (OPA) and a thio l (N-acetylcysteine, NAC), to form a derivative which can be measured fluor imetrically. To investigate the influence of the different FIA system param eters on both the peak height and the residence time for a set of 28 pharma ceutical compounds, a half-fraction factorial design for five factors at tw o levels (2(5-1): resolution V = 16 experiments) was executed. Effects on b oth responses were calculated. Since the peak height should be maximized an d the residence time minimized, the Pareto optimality concept was applied t o make an optimal compromise between both responses and to eventually selec t a generic FIA system. (C) 2001 Elsevier Science B.V. All rights reserved.