Determination of metal residues in active pharmaceutical ingredients according to European current legislation by using X-ray fluorescence spectrometry

摘要

The monitoring of heavy metals in drug substances is an important task in modern pharmaceutical laboratories. In the present work, a rapid and simple method for the determination of some inorganic impurities (Fe, Zn, Cr and Ni) in active pharmaceutical ingredients (APIs) by wavelength dispersive X-ray fluorescence spectrometry (WDXRF) has been developed and validated according to the specification limits of the European Agency for the Evaluation of Medicinal Products (EMEA) and the guidelines of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human use (ICH). The achieved results showed that the API's matrix significantly affects the determination of metals by XRF spectrometry and this fact has to be taken into consideration when selecting the best compound candidate to prepare the synthetic calibration standards for quantitation purposes. The calculated LODs and LOQs meet the rigorous limit requirements of current legislation and, hence, the use of this analytical technique is presented as an interesting alternative to the current compendial "heavy metal test" that is going to be replaced with an instrument-based approach by international pharmacopoeias in the near future.