RESUMO
Ethylene Glycol (EG) and diethylene Glycol (DEG) are two contaminants known to cause various human health problems. These glycols might be present in drug syrups that are based on glycerol, sorbitol, or polyethylene glycol. In late 2022, several batches of cough, antipyretics, and antihistamine syrups were reported to contain toxic levels of EG and DEG in multiple countries; this incident concerned the World Health Organization (WHO). From an analytical perspective, several methods of glycols analysis in pharmaceuticals have been reported in the literature, with the majority being dedicated to raw material analysis. This study aims to develop a selective method capable of evaluating a wide range of paediatric syrups in order to assess the safety of commercially available paediatric syrups currently distributed in the local market. This research introduces a method for determining glycols utilizing gas chromatography-tandem mass spectrometry (GC-MS/MS), which offers significantly higher selectivity than conventional single quadrupole gas chromatography-mass spectrometry (GC-MS). The developed method meets the current International Council for Harmonisation (ICH) guidelines for validation. The absence of any interfering peaks in both the unspiked sample of promethazine syrup and the reference standard solutions proved the method's selectivity. Furthermore, 2,2,2-trichloroethanol was used as an internal standard, and a new GC-MS/MS method was developed to analyze it. The calibration curves for EG and DEG were linear within the selected concentration range of 1-10 µg/mL. The detection limit for both EG and DEG was 400 ng/mL, while the quantification limit was 1 µg/mL. Recovery values for both EG and DEG met the accuracy acceptance criterion. Thus, the developed method proved to be efficient and accurate for determining EG and DEG levels in suspected contaminated syrups.
RESUMO
BACKGROUND: Fluoropyrimidines (FP) are among the most common class of prescribed anti-neoplastic drugs. This class has severe to moderate toxicity in around 10%-40% of those who take 5-fluorouracil (5-FU) or capecitabine for the treatment of cancer. In practice many patients with severe toxicities from FP use had dihydropyrimidine dehydrogenase (DPD) enzyme deficiency. Several studies have proposed DPD screening before treatment with 5-fluorouracil (5-FU) and capecitabine or other drugs belonging to the FP group. This study aims to assess the level of awareness and attitudes of oncology specialists in Saudi Arabia toward genetic screening for DPD prior to giving FP. This highlights the importance of health guidelines required for implementation in our health care system, as a framework to adopt testing as a regular practice in clinical care. Based on the findings in this study, guidelines have been suggested for the Middle East North Africa region. METHODS: A cross-sectional survey study was conducted during 2021 targeting oncologists and clinical pharmacists working in the oncology departments across Saudi Arabia. RESULTS: A total of 130 oncologists and pharmacists completed the questionnaire representing a response rate of 87%. Most of the respondents indicated that they prescribe FP in clinical practice, but 41% of respondents reported that they have never ordered a specific molecular test during their practice. Only 20% of respondents reported that they often screen for DPD deficiency prior to prescribing FP. Significantly higher rates of awareness of potential dihydropyrimidine dehydrogenase gene (DPYD) mutation were observed among respondents in governmental hospitals (81.1% vs. 47.4% in private hospitals), and among those with more years of practice (80.6% if 5 or more years of practice vs. 59.3% if less than 5 years of practice). Also, higher rates of observing the impact of DPD testing were present among respondents with a PharmD (35% vs. 11% for oncologists and 18% for other professions) and among those with 5 or more years of practice (24.6% vs. 7.7% among those with less than 5 years). CONCLUSION: While in some institutions there is a high level of awareness among oncology specialists in Saudi Arabia regarding the effect of the potentially serious DPD enzyme deficiency as a result of gene mutations, screening for these mutations prior to prescribing FP is not a routine practice in hospitals across the country. The findings of this study should promote personalized medicine with recognition of interpatient variability via DPD testing to manage the risks of FP prescribing more effectively in the Kingdom of Saudi Arabia.