Thiyagarajan Thilak Kumar, Abdul Hakeem Jamal Abdul Nasser, Baksam Vijayakumar
Department of Chemistry, Jamal Mohamed College, Trichirapalli, Tamilnadu, India.
J Chromatogr Sci. 2012 Nov-Dec;50(10):945-52. doi: 10.1093/chromsci/bms095. Epub 2012 Jun 11.
A high-throughput reverse-phase liquid chromatographic (RP-LC) method is developed for the quantification of zafirlukast and its related impurities in drug substance. The separation of known impurities is accomplished using a short (50 mm) LC column with sub-2-µm particle size in a relatively short run-time. A linear gradient elution involves ammonium formate and acetonitrile as mobile phase. The critical impurity pair is the meta and para isomers of zafirlukast, which are known to be potential impurities of zafirlukast, whose resolution is sensitive to pH. The stability-indicating capability of the developed method is demonstrated using forced degradation samples from stress conditions such as hydrolysis, oxidation, thermal and photolytic degradation. The developed RP-LC method is validated in accordance with International Conference on Harmonization requirements. The results from the validation study indicate that this RP-LC method can be used for the determination of synthetic and degradation impurities in regular quality control analysis for the drug substance.
开发了一种高通量反相液相色谱（RP-LC）方法，用于定量原料药中扎鲁司特及其相关杂质。使用粒径小于2μm的短（50mm）液相色谱柱，在相对较短的运行时间内完成已知杂质的分离。线性梯度洗脱采用甲酸铵和乙腈作为流动相。关键杂质对是扎鲁司特的间位和对位异构体，它们是扎鲁司特已知的潜在杂质，其分离度对pH敏感。通过水解、氧化、热降解和光解降解等强制降解样品，证明了所开发方法的稳定性指示能力。所开发的RP-LC方法按照国际协调会议的要求进行了验证。验证研究结果表明，该RP-LC方法可用于原料药常规质量控制分析中合成杂质和降解杂质的测定。
