Development and validation of a GC-MS method for the determination of ethylene glycol and diethylene glycol in pharmaceutical syrups.
- 1Centre of Compliance and Quality Control, National Pharmaceutical Regulatory Agency, Ministry of Health Malaysia, Petaling Jaya, Selangor, 46200, Malaysia. [email protected].
- 2Centre of Compliance and Quality Control, National Pharmaceutical Regulatory Agency, Ministry of Health Malaysia, Petaling Jaya, Selangor, 46200, Malaysia.
- 3Centre of Compliance and Quality Control, National Pharmaceutical Regulatory Agency, Ministry of Health Malaysia, Petaling Jaya, Selangor, 46200, Malaysia. [email protected].
Abstract
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.
Related
- Development and Validation of Low-Temperature Partitioning Extraction Methods for Multiresidue Determination of Pesticides in Soil and Surface Water
- USP Standards for Dietary Ingredients Derived from Mate and Guayusa Leaves: A Quality by Design Approach to Method Development and Validation for the Simultaneous Determination of Methylxanthines and Hydroxycinnamoylquinic Acids
- Development and validation of the analytical method for determination of residual solvents (2-propanol and n-hexane) in the drug substance Inosine Pranobex.
- Development, Validation, and Application of a Highly Sensitive RP-HPLC Method for the Determination and Release Profile Comparison of Levonorgestrel from Silicone-Based Contraceptive Implants
- Green Micelle-Enhanced Spectrofluorimetric Determination of Gefitinib in Pharmaceutical Tablets Using Cremophor RH 40: Response-Surface Optimization and Time-Dependent Density Functional Theory (TD-DFT) Interpretation
BibTeX
@article{amil2026development,
title = {{Development and validation of a GC-MS method for the determination of ethylene glycol and diethylene glycol in pharmaceutical syrups.}},
author = {Muhammad Amirul Amil and Muhammad Shahariz Mohamad Adzib and Nur Baizura Bujang and Kok Zheng Gan and Sara Khalida Jamal Khair and Malissa Wani Mohammad Amini and Ahmad Zariq Syafiq Zaire and Ahmad Yusri Mohd Yusop},
journal = {BMC pharmacology \& toxicology},
year = {2026},
month = jul,
doi = {10.1186/s40360-026-01184-2},
url = {https://europepmc.org/article/MED/42875787},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Development and validation of a GC-MS method for the determination of ethylene glycol and diethylene glycol in pharmaceutical syrups.
AU - Muhammad Amirul Amil
AU - Muhammad Shahariz Mohamad Adzib
AU - Nur Baizura Bujang
AU - Kok Zheng Gan
AU - Sara Khalida Jamal Khair
AU - Malissa Wani Mohammad Amini
AU - Ahmad Zariq Syafiq Zaire
AU - Ahmad Yusri Mohd Yusop
PY - 2026
DA - 2026/07/22
JO - BMC pharmacology & toxicology
DO - 10.1186/s40360-026-01184-2
UR - https://europepmc.org/article/MED/42875787
AB - 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.
SN - 2050-6511
ER -