A highly sensitive and interference-resistant direct injection gas chromatography (DI-GC) method for the simultaneous determination of acetonitrile and triethylamine residues in intermediate products of pneumococcal conjugate vaccines was established. The Agilent HP-5 capillary column temperature program was optimized (40 ℃ → 200 ℃) by using butanone as the internal standard. Method validation included specificity, linearity, precision, accuracy, and performance comparison with headspace gas chromatography (HS-GC). The linear ranges for acetonitrile and triethylamine were 10.25～82.0 μg/mL and 5.0～50.0 μg/mL (R2 > 0.99), respectively. The limits of detection (LOD) were 4.1 μg/mL (acetonitrile) and 2.0 μg/mL (triethylamine), with quantification limits (LOQ) of 10.25 μg/mL and 5.0 μg/mL. Spike recovery rates were 101.01% (acetonitrile) and 101.90% (triethylamine) (RSD < 3.5%), and intra-day precision RSD was < 2.0%. Acetonitrile residues in three batches ranged from 0.005% to 0.008%, while triethylamine was undetected or below 0.005%, complying with EDQM standards (acetonitrile ≤ 410 ppm, triethylamine ≤ 320 ppm). The dual-residue simultaneous detection?in vaccine intermediates, demonstrating a 60% sensitivity enhancement over HS-GC were pioneered and a robust solution for real-time quality control in vaccine manufacturing was offered.