Development and Validation of Headspace-Gas Chromatography (HS-GC) Method for the Determination of Potential Genotoxic Impurities in Meloxicam

Abstract

The development and validation of a specific Headspace-Gas Chromatography (HS-GC) method for the determination of genotoxic impurities (isopropyl chloride, propionaldehyde, 2-chloropropanol, and chloromethane) in Meloxicam. The chromatographic separation of these impurities was accomplished using a nitrogen carrier gas on a DB-624 (6% cyanopropyl phenyl + 94% dimethyl polysiloxane fused silica) (75 m x 0.53 mm, 3.0 µ) GC analytical column. The Flame Ionization Detector (FID) served as the detector with optimized temperatures set at 260°C for the detector and 240°C for the injector port. Additionally, an injection volume of 1.0 mL with a split ratio mode was employed. The performance of this method was assessed through parameters, including system suitability, specificity, linearity, range, accuracy, limit of detection (LOD), limit of quantification (LOQ) and precision. The limit of detection and limit of quantification for isopropyl chloride, propionaldehyde, 2-chloropropanol, and chloromethane were determined to be 2 and 4 ppm, respectively, and for chloromethane 0.8 and 1.6 respectively. The correlation coefficient of the linearity experiment was 0.999 for propionaldehyde, 2-chloropropanol, chloromethane and 1 for isopropyl chloride compounds. Furthermore, the accuracy assessment involved spiking the genotoxic impurities at various levels, demonstrating favourable recovery percentages well within the acceptable range of 80–120% of the limit level. These compelling results substantiate the suitability of the proposed HS-GC method for the accurate determination of isopropyl chloride, propionaldehyde, 2-chloropropanol, and chloromethane in Meloxicam.