Simultaneous Determination of Residual Palladium and Thiol Homogeneous Scavenger N-Acetylcysteine in Active Pharmaceutical Ingredients Using Inductive Coupled Plasma-Mass Spectrometry

To ensure compliance with regulations regarding levels of residual metals in pharmaceutical products, process research and development (PR&D) in the pharmaceutical industry makes wide use of metal scavengers characterized by high selectivity and effective removal ability. Thiol homogeneous scavengers are notably effective in terms of eliminating palladium from intermediates and active pharmaceutical ingredients (APIs) during production. The strategies for detecting residual thiol homogeneous scavengers such as N-acetylcysteine are presently problematic within pharmaceutical analysis. Herein a simple and effective method using inductively coupled plasma-mass spectrometry (ICP-MS) for the simultaneous detection of N-acetylcysteine (based on sulfur determination) and palladium is described. The method was successfully validated with regard to linearity, accuracy, repeatability, the limit of quantification (LOQ), and the limit of detection (LOD).

Automated summary

In order to comply with regulations on residual metal levels in pharmaceutical products, the pharmaceutical industry uses metal scavengers with high selectivity and effective removal capabilities. Thiol homogeneous scavengers are particularly effective in eliminating palladium, but detecting residual thiol homogeneous scavengers is currently problematic. A method using ICP-MS for simultaneous detection of N-acetylcysteine and palladium has been successfully validated.