Method for determination of elemental impurities in metronidazole
benzoate using inductively coupled plasma mass spectrometry
Abstract
Rationale: Metronidazole benzoate is widely used to treat a variety of
infections. The presence of elemental impurities in drug products harms
the normal physiological system without any therapeutic effects. To
ensure the quality and safety of benzoyl metronidazole, a method for the
simultaneous determination of 7 elemental impurities in metronidazole
benzoate needs to be established. Methods: Ge was used as the internal
standard element to compensate for matrix effects. The samples were
processed by direct dissolution and measured by inductively coupled
plasma mass spectrometry in kinetic energy discrimination(KED) mode. The
method was validated by USP Pharmacopoeia chapter
<233> Elemental Impurities-Procedure. Results:
The correlation coefficients of the standard curves of 7 elemental
impurities were not less than 0.999. The limits of detection were in the
range of 0.0010~0.0487 μg/g and the limits of
quantification were in the range of 0.0280 ~ 0.0306
μg/g. The recoveries were within the range of
76.5%~119.4% and the precision RSD(%) was
0.39%~1.59%(n=6). The contents of 7 elemental
impurities in the three batches of metronidazole benzoate were
originally below their limits and less than 30% of the control
threshold, in accordance with the ICH Q3D guidelines. Conclusion: This
newly developed and validated inductively coupled plasma mass
spectrometric method for estimating elemental impurities(As, Cd, Hg, Pb,
V, Vo, and Ni) in metronidazole benzoate was within the permitted limit
and suitable for routine use.