A simple, selective, and sensitive gas chromatography–mass spectrometry method for the analysis of five process‐related impurities in atenolol bulk drug and capsule formulations

Abstract

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.

Critical Analysis of Drug Product Recalls due to Nitrosamine Impurities

“…There are a number of reviews that discuss genotoxic and carcinogenic impurities in pharmaceutical products. ,,, The regulatory aspects regarding the control of impurities in drug products and their daily acceptable limits have been reviewed in the literature. ,− Regulatory guidance on impurities in drug products has also been discussed previously. Furthermore, there are a large number of reviews that discuss the analytical techniques employed in impurity profiling of drugs, including UV, FT-IR, HPLC, LC-MS/MS, headspace GC-MS/MS, LC-HRMS, NMR, LC-NMR, CE-MS, SFC-MS, ion spray-MS, CE-NMR, and LC-FT-IR. − Recently, the FDA has provided a list of product recalls due to the presence of nitrosamine impurities. However, an analysis of these recalls is not discussed in any of the reviews.…”

Development and Validation of LC-MS/MS for Analyzing Potential Genotoxic Impurities in Pantoprazole Starting Materials

“…e proposed method was validated according to the criteria of ICH guidelines [27], including specificity, linearity, LOD, LOQ, accuracy, precision, and solution stability.…”

“…Several sophisticated techniques, such as LC-mass spectrometry (MS) and gas chromatography (GC)-MS, have been used to quantify PGIs, including impurities A and B, in PPZS APIs [23][24][25]. Moreover, a number of GC-MS and UPLC-MS/MS methods for the separation and quantification of similar types of PGIs in bulk drugs and their corresponding formulations, such as rabeprazole, atenolol, darunavir, and ritonavir, have been published [26][27][28][29]. Nevertheless, to the best of our knowledge, a suitable method for the simultaneous separation and quantification of these six PGIs at the TTC level in the starting material of PPZS, i.e., DMBZ, has not been reported.…”

Sustainable Synthesis of the Active Pharmaceutical Ingredient Atenolol in Deep Eutectic Solvents

“…Atenolol belongs to the class of β-blockers and, as such, it is a selective β1 receptor antagonist [ 1 , 3 ]. It hinders the activity of substances present in the body, such as adrenaline, at the level of the heart and blood vessels, causing a consequent reduction in heart rate and blood pressure, as well as cardiac stress [ 4 ].…”