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摘要
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 2024, BIA 2059, BIA 2265, 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 2504 ChiraDex column using a mobile phase of watermethanol (92:8, v/v) pumped at 0.7mL/min. The UV detector was set at 235nm. Calibration curves were linear (r2=0.996) over the concentration ranges of 0.230 mu g/mL for oxcarbazepine, eslicarbazepine and R-licarbazepine; 0.260 mu g/mL for the remaining compounds in plasma; and 0.0615 mu g/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.
- 出版日期2012-3
