Background:
To control the potential presence of heavy metals in pharmaceuticals, the United States
Pharmacopeia (USP) and International Conference on Harmonization (ICH) have put forth new requirements and
guidelines. USP 232 and ICH Q3D specify 24 elemental impurities and their concentration limits in consideration of
the permitted daily exposure (PDE) of different drug categories (oral, parenteral and inhalation). while USP 233
describes more information about sample preparation and method validation procedure.
Objective:
To establish and verify an ICP-MS method for the determination of 24 elemental impurities (Cd, Pb, As, Hg,
Co, V, Ni, Tl, Au, Pd, Ir, Os, Ph, Ru, Se, Ag, Pt, Li, Sb, Ba, Mo, Cu, Sn, Cr) in ubenimex APIs according to USP/ICH
guidelines.
Method:
Samples were analyzed by ICP-MS after direct dissolution in diluted acid solution. All elements were detected
in He/HEHe mode (except for Li, which was in No gas mode).
Results:
The spiked recoveries were within 80-120% except Hg (79.4% at 0.5J level in HEHe mode) and Cd (121.9%
at 0.5J level in HE mode). The RSD of repeatability (N = 6) for all elements were < 7.0% and intermediate precision (N
= 12) were < 9.0%. The correlation coefficients of linear (R) for 24 elements were all > 0.998. The limits of detection
(LOD) were < 1 ng/mL except that Ni was 1.23 ng/mL in HEHe mode. The contents of 24 elements in 3 batches of
samples were significantly lower than the actual target limit of ICH, while the highest content of Pd did not exceed 10
μg/g.
Conclusion:
The established method was proved to be simple, sensitive and accurate. It successfully applied to the
elemental impurity determination in 3 batches of ubenimex APIs from different manufactories. This method also
provided technical guidance for determination of multiple elements in pharmaceutical products.
Validation and measurement uncertainty evaluation of the GC-MS method for the direct determination of hexamethylenetetramine from foods