Dorado Pedro, de Andrés Fernando, Naranjo María Eugenia G, Peñas-Lledó Eva M, González Idilio, González Antonio P, de la Rubia Alfredo, Llerena Adrián
Extremadura University Hospital amd Medical School, Badajoz, Spain.
Drug Metabol Drug Interact. 2012;27(3):165-70. doi: 10.1515/dmdi-2012-0016.
Aripiprazole (ARI) is an antipsychotic drug that is metabolized to dehydroaripiprazole (DARI) by CYP2D6. Because of the large interindividual variability in ARI and DARI plasma concentrations, therapeutic drug monitoring may be of use in psychiatric patients during treatment with ARI. The aim of the present study was to develop a simple and reliable method for the quantitative determination of ARI and DARI in plasma using liquid-liquid extraction and reverse-phase high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. The method was tested in psychiatric patients during regular treatment with ARI.
Separation was by the liquid-liquid method, and UV detection at 254 nm. Linear responses for ARI and DARI were obtained between 2 and 1000 ng/mL, and precision assays were lower than 10.4 for both analytes.
Lower limit of quantification and detection were 1 and 0.38 ng/mL for ARI and 0.78 and 0.44 ng/mL for DARI, respectively. The method was successfully applied to plasma samples drawn from 22 patients with concentrations ranging between 2 and 189 ng/mL for ARI and between 11 and 359 ng/mL for DARI.
The chromatographic method developed has been demonstrated to be sensitive and reliable for the measurement of ARI and DARI simultaneously in human plasma, and the present method represents an alternative procedure to evaluate plasma concentration in patients during treatment with ARI.
阿立哌唑（ARI）是一种抗精神病药物，通过细胞色素P450 2D6（CYP2D6）代谢为脱氢阿立哌唑（DARI）。由于ARI和DARI血浆浓度存在较大个体差异，治疗药物监测可能有助于精神科患者接受ARI治疗期间的用药。本研究的目的是开发一种简单可靠的方法，采用液液萃取和反相高效液相色谱（HPLC）结合紫外（UV）检测法定量测定血浆中的ARI和DARI。该方法在接受ARI常规治疗的精神科患者中进行了测试。
采用液液萃取法进行分离，在254 nm处进行紫外检测。ARI和DARI在2至1000 ng/mL之间呈线性响应，两种分析物的精密度测定均低于10.4。
ARI的定量下限和检测下限分别为1和0.38 ng/mL，DARI的定量下限和检测下限分别为0.78和0.44 ng/mL。该方法成功应用于22例患者的血浆样本，ARI浓度范围为2至189 ng/mL，DARI浓度范围为11至359 ng/mL。
所开发的色谱方法已被证明对同时测定人血浆中的ARI和DARI具有灵敏性和可靠性，该方法为评估接受ARI治疗患者的血浆浓度提供了一种替代方法。
