Pharmaceutical Chemistry Department, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, Egypt.
Health Research Center of Excellence, Drug Research and Development Group, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt.
Sci Rep. 2024 Oct 4;14(1):23126. doi: 10.1038/s41598-024-72822-0.
Indacaterol, a β agonist prescribed for long-term management of patients with chronic obstructive pulmonary disease and asthma. In this study the first MISPE cartridges was developed using indacaterol as a template for its selective extraction from rat lung tissues, enabling precise pharmacokinetic evaluation at the drug's site of action. A molecular imprinting polymer was synthesized using indacaterol as a template, methacrylic acid as a functional monomer and ethylene glycol dimethacrylate as a cross-linker with a molar ratio (1: 4: 20). The polymer was characterized by a high binding capacity of 9840 ± 0.86 and high selectivity with an imprinting factor of 4.53 ± 0.12. The synthesized polymer was utilized as a sorbent in solid-phase extraction to purify and extract indacaterol from lung tissue matrix. The optimum molecularly imprinted solid-phase extraction (MISPE) conditions were 20.0 mg of molecular imprinting polymer and non-imprinting polymer, acetonitrile as the loading solvent, acetonitrile: water (20: 80; by volume) as the washing solvent, and methanol: acetic acid (90: 10; by volume) as the eluting solvent. A pharmacokinetic study was performed for indacaterol in rat lungs using the synthesized and optimized MISPE cartridge as a tool for sample purification. These parameters were determined in the lung tissues of rats emphasizing the local exposure of indacaterol to its target organ. The C and T were 51.020 ± 2.810 µg mL and 0.083 ± 0.001 h, respectively. The AUC and AUC were 175.920 ± 1.053 and 542.000 ± 5.245 µg h mL, respectively. The elimination rate constant was 0.014 ± 0.00012 h and the half-life time was 48.510 ± 0.012 h. This study successfully developed and optimized MISPE cartridges using indacaterol as a template, enabling precise pharmacokinetic evaluation in rat lung tissues. The cartridges demonstrated high binding capacity and selectivity, providing crucial insights into the local exposure of indacaterol at its site of action.
吲达特罗，一种用于治疗慢性阻塞性肺疾病和哮喘患者的长效β激动剂。在这项研究中，首次开发了基于 MISPE 技术的吲达特罗萃取小柱，可选择性地从大鼠肺组织中提取药物，实现了对药物作用部位的精确药代动力学评估。采用吲达特罗为模板，甲基丙烯酸为功能单体，乙二醇二甲基丙烯酸酯为交联剂（摩尔比为 1:4:20），合成了分子印迹聚合物。聚合物的结合能力高达 9840±0.86，具有高选择性，印迹因子为 4.53±0.12。合成的聚合物被用作固相萃取中的吸附剂，用于从肺组织基质中纯化和提取吲达特罗。最佳的分子印迹固相萃取（MISPE）条件为 20.0mg 分子印迹聚合物和非印迹聚合物、乙腈为上样溶剂、乙腈：水（20:80，体积比）为洗脱溶剂、甲醇：冰醋酸（90:10，体积比）为洗脱溶剂。使用合成的优化后的 MISPE 萃取小柱作为样品净化工具，在大鼠肺中进行了吲达特罗的药代动力学研究。这些参数在大鼠肺组织中得到了确定，强调了吲达特罗在其靶器官的局部暴露情况。C 和 T 分别为 51.020±2.810µg mL 和 0.083±0.001 h，AUC 和 AUC 分别为 175.920±1.053µg h mL 和 542.000±5.245µg h mL，消除速率常数为 0.014±0.00012 h，半衰期为 48.510±0.012 h。本研究成功地以吲达特罗为模板开发并优化了 MISPE 萃取小柱，实现了对大鼠肺组织中药物的精确药代动力学评估。萃取小柱表现出高的结合能力和选择性，为吲达特罗在作用部位的局部暴露提供了关键的见解。
