An extremely sensitive and simple gas chromatography with mass spectrometry method was developed and completely validated for the analysis of five process-related impurities, viz., 4-hydroxy-l-phenylglycine, 4-hydroxyphenylacetonitrile, 4-hydroxyphenylacetic acid, methyl-4-hydroxyphenylacetate, and 2-[4-{(2RS)-2-hydroxy-3-[(1-methylethyl)amino]propoxy}phenyl]acetonitrile, in atenolol. The separation of impurities was accomplished on a BPX-5 column with dimensions of 50 m × 0.25 mm i.d. and 0.25 μm film thickness. The method validation was performed following International Conference on Harmonisation guidelines in which the method was capable to quantitate 4-hydroxy-l-phenylglycine, 4-hydroxyphenylacetonitrile, and 4-hydroxyphenylacetic acid at 0.3 ppm, and methyl-4-hydroxyphenylacetate and 2-[4-{(2RS)-2-hydroxy-3-[(1-methylethyl)amino]propoxy}phenyl]acetonitrile at 0.35 ppm with respect to 10 mg/mL of atenolol. The method was linear over the concentration range of 0.3-10 ppm for 4-hydroxy-l-phenylglycine, 4-hydroxyphenylacetonitrile, and 4-hydroxyphenylacetic acid, and 0.35-10 ppm for methyl-4-hydroxyphenylacetate and 2-[4-{(2RS)-2-hydroxy-3-[(1-methylethyl)amino]propoxy}phenyl]acetonitrile. The correlation coefficient in each case was found ≥0.998. The repeatability and recovery values were acceptable, and found between 89.38% and 105.60% for all five impurities under optimized operating conditions. The method developed here is simple, selective, and sensitive with apparently better resolution than the reported methods. Hence, the method is a straightforward and good quality control tool for the quantitation of selected impurities at trace concentrations in atenolol.
Keywords: beta-blockers; genotoxicity; mass spectrometry; method validation.
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