Fortuna Ana, Alves Gilberto, Almeida Anabela, Lopes Bruno, Falcão Amílcar, Soares-da-Silva Patrício
Pharmacology Department, Faculty of Pharmacy, University of Coimbra, 3000-548, Coimbra, Portugal.
Biomed Chromatogr. 2012 Mar;26(3):384-92. doi: 10.1002/bmc.1670. Epub 2011 Jul 21.
Recently, in silico models have been developed to predict drug pharmacokinetics. However, before application, they must be validated and, for that, information about structurally similar reference compounds is required. A chiral liquid chromatography method with ultraviolet detection (LC-UV) was developed and validated for the simultaneous quantification of BIA 2-024, BIA 2-059, BIA 2-265, oxcarbazepine, eslicarbazepine (S-licarbazepine) and R-licarbazepine in mouse plasma and brain. Compounds were extracted by a selective solid-phase extraction procedure and their chromatographic separation was achieved on a LiChroCART 250-4 ChiraDex column using a mobile phase of water-methanol (92:8, v/v) pumped at 0.7 mL/min. The UV detector was set at 235 nm. Calibration curves were linear (r(2) ≥ 0.996) over the concentration ranges of 0.2-30 µg/mL for oxcarbazepine, eslicarbazepine and R-licarbazepine; 0.2-60 µg/mL for the remaining compounds in plasma; and 0.06-15 µg/mL for all the analytes in brain homogenate. Taking into account all analytes at these concentration ranges in both matrices, the overall precision did not exceed 9.09%, and the accuracy was within ±14.3%. This LC-UV method is suitable for carrying out pharmacokinetic studies with these compounds in mouse in order to obtain a better picture of their metabolic pathways and biodistribution.
最近，已开发出计算机模拟模型来预测药物的药代动力学。然而，在应用之前，必须对其进行验证，为此，需要有关结构相似的参考化合物的信息。已开发并验证了一种具有紫外检测功能的手性液相色谱法（LC-UV），用于同时定量小鼠血浆和脑中的BIA 2-024、BIA 2-059、BIA 2-265、奥卡西平、艾司利卡西平（S-利卡西平）和R-利卡西平。通过选择性固相萃取程序提取化合物，并使用水-甲醇（92:8，v/v）流动相以0.7 mL/min的流速在LiChroCART 250-4 ChiraDex柱上实现其色谱分离。紫外检测器设置在235 nm。奥卡西平、艾司利卡西平和R-利卡西平在0.2-30 µg/mL的浓度范围内校准曲线呈线性（r(2)≥0.996）；血浆中其余化合物在0.2-60 µg/mL的浓度范围内校准曲线呈线性；脑匀浆中所有分析物在0.06-15 µg/mL的浓度范围内校准曲线呈线性。考虑到两种基质中这些浓度范围内的所有分析物，总体精密度不超过9.09%，准确度在±14.3%以内。这种LC-UV方法适用于在小鼠中对这些化合物进行药代动力学研究，以便更好地了解它们的代谢途径和生物分布情况。
