Optimized Derivatization Procedure for Characterizing (Aminomethyl)phosphonic Acid Impurities by GC-MS

The use of (aminomethyl)phosphonic acid (AMPA) as a drug substance starting material required its structurally-related impurities to be characterized in order to understand the final outcome and effect. Samples of AMPA were reacted with N,O-bis(trimethylsilyl)trifluoroacetamide with 10% trimethylchlorosilane (BSTFA + 10% TMCS) to produce volatile N- and O-trimethylsilyl derivatives. The derivatives were then analyzed by positive electron impact ionization gas chromatography mass spectrometry (EI + -GC-MS). Optimized reaction conditions (90°C, 150 min, 50 μL pyridine, 500 μL BSTFA + 10% TMCS) were obtained experimentally and with a design of experiment (DOE). This optimal derivatization procedure was applied to AMPA samples, resulting in the proposed structures of related impurities of AMPA.