Isotopic finger-printing of active pharmaceutical ingredients by 13C NMR and polarization transfer techniques as a tool to fight against counterfeiting

The robustness of adiabatic polarization transfer methods has been evaluated for determining the carbon isotopic finger-printing of active pharmaceutical ingredients. The short time stabilities of the adiabatic DEPT and INEPT sequences are very close to that observed with the one pulse sequence, but the DEPT long time stability is not sufficient for isotopic measurements at natural abundance or low enrichment. Using the INEPT sequence for ¹³C isotopic measurements induces a dramatic reduction in the experimental time without deterioration in short time or long time stability. It appears, therefore, to be a method of choice for obtaining the isotopic finger-print of different ibuprofen samples in a minimum time. The results obtained on 13 commercial ibuprofen samples from different origins show that this strategy can be used effectively to determine ¹³C distribution within a given molecule and to compare accurately differences in the isotopic distribution between different samples of the given molecule. The present methodology is proposed as a suitable tool to fight against counterfeiting.