Mat-CHN software for drug substance titrations in discovery and development

Abstract

Background: Elemental Analysis (microanalysis) is a reference method widely used to make assessments of thequality of chemical or biochemical substances. Using very small quantities of substance and no methoddevelopment, this analytical technique delivers absolute assays. Compared to other methods needing larger samplequantities and most of the time reference standards, the Elemental Analysis is the preferred technique of scientists. Methods: One of the difficulties with this method is the definition of the theoretical elemental composition when several complementary assays values, generally delivered in w/w percentages (e.g., water content by Karl Fischer method), instead of mole numbers (as this is the case for NMR determination), must be taken into account. The situation is manageable with only one of this type of additional assay; however, this exercise becomes more complicated when the scientists must integrate two or more assay values. Mat-CHN software was developed specifically to resolve these difficulties, by delivering the individual mole numberof each constituent assayed in the compound analyzed, leading to an accurate comparison of the theoretical and experimental results of centesimal compositions. Results: Apart its large capabilities for simulations, Mat-CHN increases the interest of the Elemental Analysis technique for scientists working in discovery fields or when new molecular entities are promoted to predevelopment and development stages, either for absolute titration of their reference standards or for direct titrations of the drug substance itself. The software conducts to simple titration determinations, based on Nitrogen "Kjeldhal" assays and/or molecular weight reports, compared to data of the pure substance.