Zahra Najafzadeh
1 
, Tahir Suleymanov
2, Maryam Khoubnasabjafari
3,4, Vahid Jouyban-Gharamaleki
5,6, Jalal Hanaee
7, Elaheh Rahimpour
8* , Abolghasem Jouyban
8,71 Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Pharmaceutical Chemistry, Azerbaijan Medical University, Baku, Azerbaijan
3 Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
4 Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
5 Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
6 Kimia Idea Pardaz Azarbayjan (KIPA) Science Based Company, Tabriz University of Medical Sciences, Tabriz, Iran
7 Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
8 Pharmaceutical Analysis Research Center, Pharmaceutical Sciences Institute, Tabriz University of Medical Sciences, Tabriz, Iran
Abstract
Introduction: Clonazepam is a long-acting benzodiazepine utilized for conditions such as seizures, panic disorder, and other neurological/psychiatric disorders. It functions by increasing GABA effects, which leads to reduced neural activity. Careful dosage titration and monitoring are necessary due to potential side effects, including drowsiness, impaired motor coordination, memory loss, and dependence.
Methods: In this work, an optical probe based on a terbium (Tb) coordination polymer was developed for the quantification of clonazepam in the exhaled breath condensate (EBC). The principle of the probe was based on the interaction of clonazepam with pyridine-2,6-dicarboxylic acid -Tb coordination polymer nanoparticles, which dynamically quenches the Tb³⁺ luminescence through a collisional mechanism, as confirmed by the linear Stern-Volmer plot and the increased quenching efficiency at higher temperatures. As the increase in response intensity is proportional to clonazepam concentration, a method was offered for its determination in EBC samples. Results: This method presented a linear relationship with clonazepam concentration in the range of 0.001-1.5 µg.mL-1 with a limit of detection of 0.0002 µg.mL-1 and the intra-day and inter-day relative standard deviation of 1.8%, and 2.7%, respectively. The validated method was used for clonazepam analysis in patients receiving this medication. The recovery values, ranged from 90% to 104%, served as an indicator of the method's accuracy, and confirmed that the measured signal was attributable specifically to clonazepam with high reliability.
Conclusion: By being faster, simpler, and cost-effective than traditional techniques, this method presented a valuable tool for therapeutic drug monitoring.