Development and validation of an RP-HPLC method for the quantification of residual 7-chloroquinaldine impurity in alkene aldehyde intermediate of montelukast sodium

During the synthesis of montelukast sodium drug substance from the intermediate 3-(2-(7-chloroquinolin-2-yl)-(E)-vinyl)benzaldehyde (alkene aldehyde), the purity of this intermediate is a critical factor that directly influences the overall quality and yield of the final drug product. To ensure consistent drug synthesis, strict process controls, analytical monitoring, and purification techniques must be implemented at each stage of intermediate production. With this motivation herein, a robust analytical method was developed and validated for the quantification of 7-Chloroquinaldine (7-CQ) in alkene aldehyde (AAI) in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. By improving AAI purity, manufacturers can enhance drug quality, regulatory compliance, and overall production efficiency. HPLC analysis of AAI and related impurities to 7-CQ was performed using a Shimadzu LC 2010 binary system equipped with a UV detector at 230 nm and operated via LC solution software. Separation was achieved on an XBridge C18 column (150 × 4.6 mm, 5 μm) using a gradient mobile phase of 0.075% formic acid buffer and acetonitrile. Mobile phase A was prepared in a 1:1 ratio, while mobile phase B was prepared in a 1:9 ratio. Injection volume was 10 µL, and total run time was 35 min. The validated HPLC method for 7-CQ demonstrated linearity over the concentration range of 0.49–3.72 ppm with a correlation coefficient (r) of 0.9992 and a regression coefficient (R 2 ) of 0.9983. The intercept and slope were 2415.09 ± 3348.29 and 61,762, respectively. The method exhibited high sensitivity with a limit of detection (LOD) of 0.0493 ppm and a limit of quantification (LOQ) of 0.4932 ppm. Precision was excellent, with a repeatability relative standard deviation %RSD of 0.04%, an intermediate precision % RSD of 4.57% and precision at LOQ of 5.76%. Accuracy was confirmed with recovery values ranging from 96.80% to 100% and % RSD values between 0.26% and 0.58%,demonstrating the method’s robustness, reproducibility, and suitability for routine quantitative analysis. These results confirm the reliability of the method for the routine analysis and detection of 7-CQ as an impurity in alkene aldehyde.