Studies using HPLC-PDA in gabapentin N-derivatization reactions with 9-fluorenylmethyl chloroformate (FMOC-Cl)

FMOC-Cl is a derivatizing agent widely used both in N-protection reactions of α-amino acids as well as in quantification and detection of amino acids and related molecules using HPLC-PDA or fluorescence analysis. In this work we studied the reaction of FMOC-Cl with gabapentin. However, it was observed that the degradation of gabapentin-N-FMOC and FMOC-Cl to FMOC-OH occur simultaneously in presence of the basic reaction medium which is specific for gabapentin derivatization. The degradation reaction is accelerated in temperatures above 45 °C and also by the time of contact of the reactant and product with basic medium. In this study, gabapentin derivatization reactions were shown to be cleaner and more efficient when an FMOC-Cl/gabapentin ratio of 2:1 was used, at 25 °C over a period of 15 minutes.

Keywords:
gabapentin; derivatization; degradation; FMOC-Cl; FMOC-OH; HPLC-PDA