<p>Impurity G, also known as 3-Chloro-<i>N</i>,<i>N</i>-dimethylpropan-1-amine, is a genotoxic impurity that may be present in benzydamine hydrochloride and can cause damage to genetic material, so its content must be estimated. Development of analytical methods for quantifying impurity G in benzydamine hydrochloride is a challenge, mainly because its control is at trace levels. This work applies the concepts of analytical quality by design (AQbD), measurement uncertainty, and the green chemistry approach to determine the content of impurity G in benzydamine hydrochloride using gas chromatography coupled to the flame ionization detector (GC-FID) and liquid–liquid extraction (LLE). Initially, screening was carried out using Plackett–Burman and followed by optimization with the central composite design (CCD). Response surface methodology was used to define the method operable design region, ensuring optimal performance and the definition of robust methods. Optimized conditions included a DB-624 chromatographic column (30&#xa0;m × 0.53&#xa0;mm × 3&#xa0;µm), direct splitless injection, a flow rate of 8.5&#xa0;mL/min, and helium as the carrier gas. Sample preparation used either n-heptane (4&#xa0;µL) or ethyl acetate (3&#xa0;µL) as the extraction solvent. The validated methods demonstrated selectivity, linearity (2.5–6.0&#xa0;ppm), precision, and accuracy. The green metrics (AGREE tool) using ethyl acetate in sample preparation were greener (0.73) than n-heptane (0.67) and the Ph. Eur. method (0.45). To demonstrate applicability under real analytical conditions, three independent API batches were analyzed, yielding impurity levels of 0, 3, and 4&#xa0;ppm, thereby confirming the method’s capability for reliable quantification at trace levels. Measurement uncertainties were also evaluated, showing acceptance limits (AL) for GC-FID procedures using n-heptane and ethyl acetate as extractors of 4.25 ppm (g = 0.75) and 4.75ppm (g = 0.25), respectively</p>