Development and validation of a GC-MS method for the determination of ethylene glycol and diethylene glycol in pharmaceutical syrups.

Contamination of pharmaceutical syrups with ethylene glycol (EG) and diethylene glycol (DEG) has led to serious poisoning incidents worldwide, highlighting the necessity for strong regulations and reliable testing methods. A gas chromatography-mass spectrometry (GC-MS) method was developed and validated in accordance with ICH Q2(R2) guidelines. The method was developed for pharmaceutical syrup matrices and validated using multiple commercially available products, supporting its applicability for routine regulatory surveillance. It exhibited excellent linearity, with r² of 0.9991 for EG and 0.9963 for DEG. The detection (LOD) and quantification (LOQ) limits were 0.02% v/v and 0.06% v/v, respectively, below the regulatory limit of 0.10% set by the National Pharmaceutical Regulatory Agency (NPRA), Ministry of Health Malaysia. Accuracy ranged from 94.2% to 108.4%, and the %RSD for intermediate precision was 1.4% for EG and 2.5% for DEG, confirming the method's reproducibility. When the validated method was applied to 51 pharmaceutical syrup samples available in the Malaysian market as part of post-market surveillance, 13 samples were detected to have EG. Of these, 11 samples had EG concentrations between the LOD and the LOQ, while two samples (PS-13 and PS-26) had measurable levels at 0.09% v/v. DEG was not detected in any sample. Therefore, this study emphasises the importance of regulatory surveillance, supported by validated analytical testing, to ensure the quality and safety of pharmaceutical syrups. Strengthening local surveillance mechanisms will further strengthen NPRA's regulatory capacity and safeguard public health.